It is of great significance to find safe and effective radiosensitizers.A primary investigation has been made on fisetin's modification of radiation effect,but its radiosensitization and related mechanisms still n...It is of great significance to find safe and effective radiosensitizers.A primary investigation has been made on fisetin's modification of radiation effect,but its radiosensitization and related mechanisms still need to be deeply clarified.Furthermore,fisetin with high hydrophobicity is difficult to dissolve in water,severely limiting its research and application.In this study,we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β(PDGFRβ)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)/B cell lymphoma 2(Bcl-2)signaling pathway in the tumor.Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo.On the cellular level,fisetin micelles selectively increased the radiosensitivity of tumor cells(CT26 and 4T1 cells)and had little effect on the sensitivity of normal mouse cells(L929 cells)to radiation.In the mouse models of colon and breast cancers,fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity.Additionally,we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity.In general,this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo,but also profoundly explored its mechanisms underlying,to provide a theoretical and experimental basis for the clinical application of fisetin micelles.展开更多
AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus ...AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.展开更多
Objective:To observe the chitooligosaccharides(COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line.Mothods:CCK-8 assay was employed to obtain the inhibitio...Objective:To observe the chitooligosaccharides(COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line.Mothods:CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells,MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells.The clonogenic assay was used to detect the cell viability of 0,1,2,4,6 and 8 Gy(6 dose grades) in RAY group and RAY+COS group after X-ray,and the cell survival curve was used to analyze the sensitization enhancement ratio of COS.Flow cytometry was employed to detect cell cycle and apoptosis rate in control group,RAY group and RAY+COS group after 48 h treatment.Results:COS inhibited the proliferation of three types of cells.The inhibition rate was positively correlated with the concentration of COS,and the susceptibility of MKN45 cells,SGC7901 cells and BGC823 cells to COS decreased in turn.The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY+COS group(P<0.01).The cell viabilities of RAY+COS group were lower than those of RAY group at all the dose grades under X-ray exposure(P<0.01),and the sensitization enhancement ratios of COS on BGC823 cells,MKN45 cells and SGC7901 cells were 1.06,1.28 and 1.15 respectively.In controlled trials,apoptosis rate and percentage in the G_2/M phase of three types of cells in RAY+COS group were higher than those in control group and RAY group,and percentage in the S phase and the G_0/G_1 phase in RAY+COS group were lower than those in the other two groups(P<0.01).Conclusions:COS can inhibit the proliferation of three types of human gastric cancer cells and enhance the radiosensitivity by inducing apoptosis and G_2/M phase arrest.展开更多
Objective: To observe the anti-proliferation and radiosensitization effect of chitooligosaccharides(COS) on human lung cancer cell line Hep G2. Methods: CCK-8 assay was employed to obtain the inhibition ratio of COS o...Objective: To observe the anti-proliferation and radiosensitization effect of chitooligosaccharides(COS) on human lung cancer cell line Hep G2. Methods: CCK-8 assay was employed to obtain the inhibition ratio of COS on Hep G2 cells at 24 h after treatment. The clonogenic assay was used to analyze the cell viability of RAY group and RAY+COS group with X-ray of 0, 1, 2, 4, 6 and 8 Gy, and the cell survival curve was used to analyze the sensitization ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY+COS group after 24 h treatment. Results: COS inhibited the proliferation of Hep G2 cells, and the inhibition rate positively correlated with the concentration of COS. The cell viability decreased with increasing exposure dose in RAY group and RAY+COS group. The cell viabilities of RAY+COS group were lower than those of RAY group at the dose of 4, 6 and 8 Gy(P<0.05), and the sensitization ratio of COS was 1.19. There were higher percentage at G2/M phase and apoptosis rate, and lower percentage at S phase in RAY+COS group versus the other two groups(P<0.01). Conclusions: COS can inhibit the proliferation of Hep G2 cells, and enhance the radiosensitization of Hep G2 cells, induce apoptosis and G2/M phase arrest.展开更多
This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuc...This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuclear cell direct cytotoxicity assay(MTT) in vitro.HeLa cells were treated by cisplatin/docetaxel of 10 percent of IC20 alone or combined with LY294002 for 24 h,and then radiated by different doses of X-ray.The cell survival ratio was obtained by means of clone formation.One-hit multi-target model was fitted to the cell survival curve to calculate dose quasithreshold(Dq),mean lethal dose(D0),2Gy survival fraction(SF2) and sensitization enhancement ratio(SER).The pAkt and total Akt expression was detected by Western blotting and DNA damage by neutro-comet electrophoresis.The HeLa cells were randomly divided into 7 groups in terms of different treatments:Control;radiation treatment(RT) group;LY294002+RT group;cisplatin+RT group;docetaxel+RT group;LY294002+cisplatin+RT group;LY294002+docetaxel+RT group.The apoptosis ratio of each group was measured by flow cytometry.The results showed that docetaxel and cisplatin significantly enhanced the phosphorylation of Akt in radiation-treated HeLa cells.The Dq,D0 and SF2 in LY294002-contained groups were lower than those in docetaxel or cisplatin+RT group.The SER in the LY294002+docetaxel+RT group was 1.35 times that of the docetaxel+RT group,and that in the LY294002+cisplatin+RT group 1.26 times that of the cisplatin+RT group.The Comet electrophoresis showed that tail distance in the LY294002+cisplatin+RT group or LY294002+docetaxel+RT group was longer than in the cisplatin+RT group or docetaxel+RT group.The apoptosis ratio in the LY294002+cisplatin+RT group or LY294002+docetaxel +RT group was higher than in the cisplatin+RT group or docetaxel+RT group.It was concluded that inhibiting PI3K/Akt pathway can increase the effect of docetaxel and cisplatin on the radiosensitivity of HeLa cells and DNA damage resulted from radiation.展开更多
Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective the...Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS)expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.展开更多
AIM: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.METHODS: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L ...AIM: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.METHODS: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time. RESULTS: The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h.CONCLUSION: A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.展开更多
Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation ene...Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.展开更多
Objective:To explore the role of cyclophilin A(CyPA)in sensitization of lung adenocarcinoma to radiotherapy using CRISPR/Cas9 technology.Methods:A CyPA knockout human lung adenocarcinoma cell line H1975 was establishe...Objective:To explore the role of cyclophilin A(CyPA)in sensitization of lung adenocarcinoma to radiotherapy using CRISPR/Cas9 technology.Methods:A CyPA knockout human lung adenocarcinoma cell line H1975 was established by CRISPR/Cas9 technology.Groups included a control group(wildtype),CyPA knockout group,traditional Chinese medicine(TCM)extract with Fuzhengzengxiao decoction group,and TCM extract with Fuzhengzengxiao decoction t CyPA knockout group.Each group was exposed to radiation at doses of 0,2,4,6,and 8 Gy.After 24 h,MTT assays were used to determine the survival rate of lung cancer cells and calculate radiosensitivity.The qPCR was used to measure mRNA expression of DDIT3,CDKN1A,and CDC25A associated with DNA damage repair.Results:Without irradiation,Fuzhengzengxiao decoction reduced the survival rate of lung adenocarcinoma cells(P<.0001).After irradiation,TCM extract with Fuzhengzengxiao decoction,CyPA knockout,and TCM extract with Fuzhengzengxiao decoction t CyPA knockout groups had reduced survival rates(P<.0001)and radiosensitivity was increased significantly.Expression of DDIT3,CDKN1A,and CDC25A was upregulated after knockout of CyPA(P<.0001).Expression of DDIT3 and CDC25A was increased after irradiation in wildtype cells treated with TCM extract with Fuzhengzengxiao decoction(DDIT3,P<.0001;CDC25A,P紏.0059).The TCM extract with Fuzhengzengxiao decoction t CyPA knockout group also had increased expression of DDIT3 and CDC25A after irradiation(P<.0001).Conclusion:Fuzhengzengxiao decoction significantly decreases the survival rate of lung cancer cells,and its mechanism may be related to radiosensitization by decreasing expression of CyPA and inducing G1/S cell cycle arrest.展开更多
Nanoparticles(NPs) with high-Z atoms have been widely studied as radiosensitizers for use in cancer therapy. Over the past few years, the application of FePt NPs has attracted extensive research interest. Promising re...Nanoparticles(NPs) with high-Z atoms have been widely studied as radiosensitizers for use in cancer therapy. Over the past few years, the application of FePt NPs has attracted extensive research interest. Promising results have been obtained, yet limited knowledge is available regarding its potential use as a radiosensitizer.The goal of this study is to investigate the radiosensitization capability of FePt nanoparticle clusters(NPCs) under the exposure of kilovoltage photons using Monte Carlo simulation. First, in order to obtain a realistic distribution of NPCs on the microscopic level, Hela cells were incubated with FePt NPs, and the distribution of NPCs was obtained by optical microscope images and X-ray NanoCT experiments. Based on these images, a simplified cellmodel was developed to evaluate the DER of two material types(FePt and FePt_3). For each type, the dependence of DER on the thickness and angular distribution of NPCs on the surface of the cell membrane was studied quantitatively. Our results suggest that DER is strongly dependent on photon energy and the distance from the NPCs to the nucleus. Fe_1 Pt_3 is able to achieve a higher DER relative to Fe_1 Pt_1. For a given X-ray energy, DER demonstrates an initial increase to a maximum value but gradually saturates as the thickness of NPCs increases from 250 up to 2000 nm due to a trapping effect. The impact on DER resulting from the coexistence of the NPCs on the cell membrane and the nuclear membrane was also investigated.展开更多
Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stabl...Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stable upregulation or downregulation of mir-30a-5p,and their negative control,were transfected with lentivirus vectors.These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft.Each group was randomly divided into irradiated and non-irradiated groups.The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight.The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins,using immunohistochemistry and Western blotting.Results The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control(lenti-GFP)group and lower in the lenti-inhibitor group(P<0.05).Subcutaneous lung-cancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly;tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups.In contrast,the opposite of these effects was observed in the lenti-inhibitor group.Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group,with or without irradiation,compared to that in the lenti-GFP group.ATM protein levels were higher in the lenti-inhibitor groups.The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation(P<0.05).Moreover,the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation(P<0.05).Conclusion Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.展开更多
Telomerase inhibitor MST-312 is a new compound derived from epigallocatechin gallate (EGCG)[1]. Our resultsdemonstrated that 4 M MST-312 not only showed lower cytotoxicity, but also inhibited telomerase activity inHe...Telomerase inhibitor MST-312 is a new compound derived from epigallocatechin gallate (EGCG)[1]. Our resultsdemonstrated that 4 M MST-312 not only showed lower cytotoxicity, but also inhibited telomerase activity inHepG2 cells. Therefore, in our experiments, 4 M MST-312 was chosen to study radiosensitization and relatedmechanisms. -H2AX foci are considered as an indicator of DNA damages[2]. The immunofluorescence stainingresults showed the number of -H2AX foci in the pretreatment with MST-312 followed by 2 Gy X-ray irradiationgroup. However, as shown in Fig. 1, the formation of Rad51 foci in the combined treatment group was blockedoutside the nuclear of HepG2 cells, when compared with the irradiation alone group. JC-1 staining showed thatMST-312 pretreatment, followed by X-ray irradiation, caused increase of the green/red fluorescence intensity ratio(ΔΨm) compared with X-ray irradiation alone. Meanwhile, MST-312 pretreatment followed by X-ray irradiationelevated expression of p53 protein and decreased expression of caspase-3 as well as fraction of Bcl-2 / Bax.展开更多
Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determine...Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries,whether surface ligands can affect their radiosensitization has seldom been investi-gated in the radiosensitization of AuNPs.By conducting head-to-head comparison on radio-sensitization of two kinds of ultrasmall(~2 nm)near-infrared(NIR)emitting AuNPs that are coated with zwitterionic glutathione and neutr al polyethylene glyol(PEG)ligands,respectively,we found that zwitterionic glut athione coated AuNPs(GS-AuNPs)can reduce survival rates of MCF-7 cells under irr adiation of clinically used megavoltage photon beam at low dosage of~2.25 Gy.On the other hand,PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation,clearly indicating the key role of surface cheistry in radiosensitization of AuNPs.More detailed studies suggested that such difference was inde-pendent of cellular uptake and its eficiency,but might be related to the ligand-induced difference in photoelectron generation and/or inter actions between AuNPs and X-ray triggered reactive oxygen species(ROS).展开更多
Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and F...Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and Fe particle irradiation.Methods:The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells.A549 and NCI-H460 cells,human non-small cell lung cancer(NSCLC)cell lines,were irradiated with X-ray or high linear energy transfer(LET)irradiation with or without ANTP-SMACN7 treatment.Cellular survival,apoptosis,and protein expression were studied by colony formation assays,flow cytometry,and western blot analyses,respectively.Results:ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization.High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis(P<0.05).Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9.Conclusions:Regarding pharmaceutical radiosensitization,these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.展开更多
Current radiotherapy(RT)lacks the ability to accurately discriminate between tumor and healthy tissues,resulting in significant radiation-induced damage for patients.Therefore,there is an urgent need for precise RT te...Current radiotherapy(RT)lacks the ability to accurately discriminate between tumor and healthy tissues,resulting in significant radiation-induced damage for patients.Therefore,there is an urgent need for precise RT techniques that can optimize tumor control while minimizing adverse effects on surrounding healthy tissues.In this study,we developed a nanodrug(AuNR@Peptide)composed of furin-responsive RVRR peptide-conjugated AuNRs,which integrates an activatable probe and a radiosensitizer into a single system for accurate tumor localization,enabling imageguided precision RT.Upon reaching the tumor site after intravenous administration,proteolytic cleavage of RVRR substrates on AuNR@Peptide by biomarker triggers aggregation of gold nanorods(AuNRs)into larger aggregates,leading to activation of near-infrared(NIR)-II photoacoustic(PA)signals to precisely localize the tumor and enhance tumor retention by preventing migration and backflow of AuNRs.This significantly amplifies radiosensitivity efficiency.The peak time point at which the NIR-II PA signal was observed at the tumor site after injection serves as a reference for initiating RT,demonstrating substantial improvement in tumor RT through investigations related to radiosensitization mechanisms.The integration of imaging and therapy in this study offers a promising image-guided therapeutic modality for tumors.展开更多
Riboflavin, suggested to be a radiosensitizer, was studied in murine thymocytes and human hepatoma L02 cell line in vitro with MTT method and fluorescence microscopy. When the murine thymocytes treated with 5-400 μmo...Riboflavin, suggested to be a radiosensitizer, was studied in murine thymocytes and human hepatoma L02 cell line in vitro with MTT method and fluorescence microscopy. When the murine thymocytes treated with 5-400 μmol/L riboflavin were irradiated by 5 Gy 60Co γ ionizing radiation, the low concentration groups, i.e. treated with 5-50 μmol/L riboflavin, showed a different surviving fractions-time relating correlation compared with the high concentration groups, i.e. treated with 100-400 μmol/L riboflavin. The former had a high survival level at the end of irradiation, but which, after 4-h incubation, decreased rapidly to a low level. On the contrary, the high concentration groups showed a low survival level at the end of irradiation, and a poor correlation was found between the surviving fraction and the incubation time, after 4 h a little difference was observed. The results of fluorescence microscopy indicated that under low concentration conditions, the riboflavin localized mainly in nucleus (both perinuclear area and inside of nuclear membrane), while under high concentration conditions, intensive riboflavin also localized around cytoplasmic membranes. Thus we can conclude: the riboflavin had radiosensitivity effect on DNA under low concentration conditions, and enhanced the damage to cytoplasmic membrane under high concentration conditions. Also the most effective concentration of riboflavin can be evaluated to be approximate 100 μmol/L.展开更多
Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 ...Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 and cell cloning experiments were applied to evaluate the effects of SPE on the proliferation of CNE-2R cells,and a single-hit multitarget model was used to calculate the radiobiological parameters.Cell apoptosis and cell cycle were analyzed by flow cytometry,and the levels of genes and proteins of the Raf/MEK/ERK pathway were determined by RT-PCR and Western blotting.Results:A total of 37 compounds from SPE were identified,and SPE with or without irradiation inhibited the proliferation of CNE-2R cells.SPE also promoted apoptosis,arrested cells in the G_(2)/M phase,and presented radiosensitizing effects.Compared with irradiation alone,the effects of SPE+irradiation on apoptosis and cell cycle distribution were not significantly different.In addition,SPE had no significant effect on MEK gene expression.SPE significantly increased the gene expression of C-Raf and significantly reduced the protein expression of C-Raf,as well as the gene and protein expression of ERK1 and ERK2.The protein levels of C-Raf,ERK1,and ERK2 were also significantly lower in cells treated with SPE+irradiation than in cells treated with irradiation alone.Conclusions:The effects of SPE on inhibiting cell proliferation and promoting apoptosis are likely associated with cell cycle arrest and Raf/MEK/ERK pathway regulation,and the mechanism underlying radiosensitization by SPE may involve downregulating the protein expression of C-Raf,ERK1,and ERK2.展开更多
Colorectal cancer(CRC)remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages.Despite advancements in early screening...Colorectal cancer(CRC)remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages.Despite advancements in early screening and therapeutic interventions,the outcomes of patients with advanced-stage CRC remain suboptimal,as these patients continue to exhibit a persistently low 5-year survival rate.Palliative radiotherapy(RT)is crucial for advanced CRC patients,but radioresistance remains a significant clinical challenge.This resistance is attributed to multiple mechanisms,such as genetic heterogeneity,dysregulated DNA damage repair and tumor microenvironment metabolic disorders.Recent studies have shown that noncoding RNAs(ncRNAs),mainly microRNAs,long ncRNAs(lncRNAs)and circular RNAs,play pivotal roles in regulating CRC radiosensitivity through diverse mechanisms,such as epithelial-mesenchymal transition,epigenetic reprogramming,posttranscriptional regulation and oncogenic signaling pathway activation.For example,microRNAs such as miR-141-3p and miR-630 enhance CRC radiosensitivity by targeting oncogenic pathways.In addition,lncRNAs,including the lncRNAs HOTAIR and LINC00630,influence the radiosensitivity of CRC through interactions with the DNA damage repair machinery and epigenetic modulators,respectively.In addition,circ_0124554 acts as a competitive endogenous RNA to regulate oncogenic signaling.ncRNAs also serve as potential biomarkers for predicting radiosensitivity and prognosis.This review synthesizes the current evidence on the ncRNA-mediated regulatory networks that influence CRC radiosensitivity,emphasizing their potential as therapeutic targets to overcome RT resistance and improve outcomes in advanced CRC.By bridging mechanistic insights with clinical applications,this work aims to guide future research and the implementation of precision RT strategies.展开更多
BACKGROUND Esophageal cancer(ESCA)poses a significant challenge in oncology because of the limited treatment options and poor prognosis.Therefore,enhancing the therapeutic effects of radiotherapy for ESCA and identify...BACKGROUND Esophageal cancer(ESCA)poses a significant challenge in oncology because of the limited treatment options and poor prognosis.Therefore,enhancing the therapeutic effects of radiotherapy for ESCA and identifying relevant therapeutic targets are crucial for improving both the survival rate and quality of life of patients.AIM To define the role of the transcription factor Snail family transcriptional repressor 1(SNAI1)in ESCA,particularly its regulation of radiosensitivity.METHODS A comprehensive analysis of TCGA data assessed SNAI1 expression in ESCA.Survival curves correlated SNAI1 levels with radiotherapy outcomes.Colony formation assays,flow cytometry,and a xenograft model were used to evaluate tumor radiosensitivity and apoptosis.Western blot validated protein expression,while Chromatin im-munoprecipitation assays examined SNAI1's role in regulating epithelial-mesenchymal transition(EMT).RESULTS SNAI1 expression in ESCA cell lines and clinical specimens emphasizes its central role in this disease.Elevated SNAI1 expression is correlated with unfavorable outcomes in radiotherapy.Downregulation of SNAI1 enhances the sensitivity of ESCA cells to ionizing radiation(IR),resulting in remarkable tumor regression upon IR treatment in vivo.This study underscores the direct involvement of SNAI1 in the regulation of EMT,particularly under IR-induced conditions.Furthermore,inhibiting deacetylation effectively suppresses EMT,suggesting a potential avenue to enhance the response to radiotherapy in ESCA.CONCLUSION This study highlights SNAI1's role in ESCA radiosensitivity,offering prognostic insights and therapeutic strategies to enhance radiotherapy by targeting SNAI1 and modulating EMT processes.展开更多
基金funded by a grant from Technology Project of Science and technology department of Sichuan province(No.2018SZ0021)。
文摘It is of great significance to find safe and effective radiosensitizers.A primary investigation has been made on fisetin's modification of radiation effect,but its radiosensitization and related mechanisms still need to be deeply clarified.Furthermore,fisetin with high hydrophobicity is difficult to dissolve in water,severely limiting its research and application.In this study,we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β(PDGFRβ)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)/B cell lymphoma 2(Bcl-2)signaling pathway in the tumor.Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo.On the cellular level,fisetin micelles selectively increased the radiosensitivity of tumor cells(CT26 and 4T1 cells)and had little effect on the sensitivity of normal mouse cells(L929 cells)to radiation.In the mouse models of colon and breast cancers,fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity.Additionally,we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity.In general,this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo,but also profoundly explored its mechanisms underlying,to provide a theoretical and experimental basis for the clinical application of fisetin micelles.
文摘AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.
基金supported by Youth Science Fund Project(No.81400612)
文摘Objective:To observe the chitooligosaccharides(COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line.Mothods:CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells,MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells.The clonogenic assay was used to detect the cell viability of 0,1,2,4,6 and 8 Gy(6 dose grades) in RAY group and RAY+COS group after X-ray,and the cell survival curve was used to analyze the sensitization enhancement ratio of COS.Flow cytometry was employed to detect cell cycle and apoptosis rate in control group,RAY group and RAY+COS group after 48 h treatment.Results:COS inhibited the proliferation of three types of cells.The inhibition rate was positively correlated with the concentration of COS,and the susceptibility of MKN45 cells,SGC7901 cells and BGC823 cells to COS decreased in turn.The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY+COS group(P<0.01).The cell viabilities of RAY+COS group were lower than those of RAY group at all the dose grades under X-ray exposure(P<0.01),and the sensitization enhancement ratios of COS on BGC823 cells,MKN45 cells and SGC7901 cells were 1.06,1.28 and 1.15 respectively.In controlled trials,apoptosis rate and percentage in the G_2/M phase of three types of cells in RAY+COS group were higher than those in control group and RAY group,and percentage in the S phase and the G_0/G_1 phase in RAY+COS group were lower than those in the other two groups(P<0.01).Conclusions:COS can inhibit the proliferation of three types of human gastric cancer cells and enhance the radiosensitivity by inducing apoptosis and G_2/M phase arrest.
文摘Objective: To observe the anti-proliferation and radiosensitization effect of chitooligosaccharides(COS) on human lung cancer cell line Hep G2. Methods: CCK-8 assay was employed to obtain the inhibition ratio of COS on Hep G2 cells at 24 h after treatment. The clonogenic assay was used to analyze the cell viability of RAY group and RAY+COS group with X-ray of 0, 1, 2, 4, 6 and 8 Gy, and the cell survival curve was used to analyze the sensitization ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY+COS group after 24 h treatment. Results: COS inhibited the proliferation of Hep G2 cells, and the inhibition rate positively correlated with the concentration of COS. The cell viability decreased with increasing exposure dose in RAY group and RAY+COS group. The cell viabilities of RAY+COS group were lower than those of RAY group at the dose of 4, 6 and 8 Gy(P<0.05), and the sensitization ratio of COS was 1.19. There were higher percentage at G2/M phase and apoptosis rate, and lower percentage at S phase in RAY+COS group versus the other two groups(P<0.01). Conclusions: COS can inhibit the proliferation of Hep G2 cells, and enhance the radiosensitization of Hep G2 cells, induce apoptosis and G2/M phase arrest.
基金supported by grants from the Hubei Province Natural Sciences Foundation (No.2008cdb133)Science Foundation for The Youth Scholars of Ministry of Education of China (No.200804871034)
文摘This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuclear cell direct cytotoxicity assay(MTT) in vitro.HeLa cells were treated by cisplatin/docetaxel of 10 percent of IC20 alone or combined with LY294002 for 24 h,and then radiated by different doses of X-ray.The cell survival ratio was obtained by means of clone formation.One-hit multi-target model was fitted to the cell survival curve to calculate dose quasithreshold(Dq),mean lethal dose(D0),2Gy survival fraction(SF2) and sensitization enhancement ratio(SER).The pAkt and total Akt expression was detected by Western blotting and DNA damage by neutro-comet electrophoresis.The HeLa cells were randomly divided into 7 groups in terms of different treatments:Control;radiation treatment(RT) group;LY294002+RT group;cisplatin+RT group;docetaxel+RT group;LY294002+cisplatin+RT group;LY294002+docetaxel+RT group.The apoptosis ratio of each group was measured by flow cytometry.The results showed that docetaxel and cisplatin significantly enhanced the phosphorylation of Akt in radiation-treated HeLa cells.The Dq,D0 and SF2 in LY294002-contained groups were lower than those in docetaxel or cisplatin+RT group.The SER in the LY294002+docetaxel+RT group was 1.35 times that of the docetaxel+RT group,and that in the LY294002+cisplatin+RT group 1.26 times that of the cisplatin+RT group.The Comet electrophoresis showed that tail distance in the LY294002+cisplatin+RT group or LY294002+docetaxel+RT group was longer than in the cisplatin+RT group or docetaxel+RT group.The apoptosis ratio in the LY294002+cisplatin+RT group or LY294002+docetaxel +RT group was higher than in the cisplatin+RT group or docetaxel+RT group.It was concluded that inhibiting PI3K/Akt pathway can increase the effect of docetaxel and cisplatin on the radiosensitivity of HeLa cells and DNA damage resulted from radiation.
基金supported by grants from the Shanghai Municipal Commission of Health and Family Planning(No.2017YQ052)the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(No.2017QNRC061)+3 种基金the National Natural Science Foundation of China(Nos.81673352,81872453)the Bio-Pharmaceutical Project of Science and Technology of Shanghai(No.15431901700)the Natural Science Foundation of Shanghai(No.18ZR1438700)the Key Research and Development Program of Ningxia(Nos.2018BFH02001 and 2019BFG02017)。
文摘Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS)expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.
文摘AIM: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.METHODS: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time. RESULTS: The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h.CONCLUSION: A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.
基金supported by the National Natural Science Foundation of China(No.82172186)the Zhejiang Provincial Natural Science Foundation of China(No.LY21H160030)+1 种基金the National Natural Science Foundation of China(No.82373206,No.82073332)the National Key Research and Development Program of China(No.2022YFE0107800).
文摘Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.
基金This work was supported by NSFC project(No.81573736).
文摘Objective:To explore the role of cyclophilin A(CyPA)in sensitization of lung adenocarcinoma to radiotherapy using CRISPR/Cas9 technology.Methods:A CyPA knockout human lung adenocarcinoma cell line H1975 was established by CRISPR/Cas9 technology.Groups included a control group(wildtype),CyPA knockout group,traditional Chinese medicine(TCM)extract with Fuzhengzengxiao decoction group,and TCM extract with Fuzhengzengxiao decoction t CyPA knockout group.Each group was exposed to radiation at doses of 0,2,4,6,and 8 Gy.After 24 h,MTT assays were used to determine the survival rate of lung cancer cells and calculate radiosensitivity.The qPCR was used to measure mRNA expression of DDIT3,CDKN1A,and CDC25A associated with DNA damage repair.Results:Without irradiation,Fuzhengzengxiao decoction reduced the survival rate of lung adenocarcinoma cells(P<.0001).After irradiation,TCM extract with Fuzhengzengxiao decoction,CyPA knockout,and TCM extract with Fuzhengzengxiao decoction t CyPA knockout groups had reduced survival rates(P<.0001)and radiosensitivity was increased significantly.Expression of DDIT3,CDKN1A,and CDC25A was upregulated after knockout of CyPA(P<.0001).Expression of DDIT3 and CDC25A was increased after irradiation in wildtype cells treated with TCM extract with Fuzhengzengxiao decoction(DDIT3,P<.0001;CDC25A,P紏.0059).The TCM extract with Fuzhengzengxiao decoction t CyPA knockout group also had increased expression of DDIT3 and CDC25A after irradiation(P<.0001).Conclusion:Fuzhengzengxiao decoction significantly decreases the survival rate of lung cancer cells,and its mechanism may be related to radiosensitization by decreasing expression of CyPA and inducing G1/S cell cycle arrest.
基金supported by the Natural Science Foundation of China(Nos.10875092 and 31271511)the Natural Science Foundation of Hubei Province of China(No.2012KB04449)
文摘Nanoparticles(NPs) with high-Z atoms have been widely studied as radiosensitizers for use in cancer therapy. Over the past few years, the application of FePt NPs has attracted extensive research interest. Promising results have been obtained, yet limited knowledge is available regarding its potential use as a radiosensitizer.The goal of this study is to investigate the radiosensitization capability of FePt nanoparticle clusters(NPCs) under the exposure of kilovoltage photons using Monte Carlo simulation. First, in order to obtain a realistic distribution of NPCs on the microscopic level, Hela cells were incubated with FePt NPs, and the distribution of NPCs was obtained by optical microscope images and X-ray NanoCT experiments. Based on these images, a simplified cellmodel was developed to evaluate the DER of two material types(FePt and FePt_3). For each type, the dependence of DER on the thickness and angular distribution of NPCs on the surface of the cell membrane was studied quantitatively. Our results suggest that DER is strongly dependent on photon energy and the distance from the NPCs to the nucleus. Fe_1 Pt_3 is able to achieve a higher DER relative to Fe_1 Pt_1. For a given X-ray energy, DER demonstrates an initial increase to a maximum value but gradually saturates as the thickness of NPCs increases from 250 up to 2000 nm due to a trapping effect. The impact on DER resulting from the coexistence of the NPCs on the cell membrane and the nuclear membrane was also investigated.
基金supported by the National Science Fund Project (No. 81872471)the National Natural Science Foundation of China and the Science Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University (No. YJ(QN)202025)
文摘Objective We aimed to observe the radiosensitization effect of mir-30a-5p in a nude mouse model with subcutaneous lung-cancer xenograft and to explore the underlying mechanism.Methods A549 cell lines with either stable upregulation or downregulation of mir-30a-5p,and their negative control,were transfected with lentivirus vectors.These cell lines were used to establish a nude mouse model with subcutaneous lung-cancer xenograft.Each group was randomly divided into irradiated and non-irradiated groups.The radiosensitization effect of mir-30a-5p in vivo was studied by observing xenograft growth trends and tumor weight.The mechanisms involved in this radiosensitization were investigated by detecting expressed radiosensitization-related proteins,using immunohistochemistry and Western blotting.Results The expression level of mir-30a-5p in the lenti-mir-30a-5p group was higher than that in the negative control(lenti-GFP)group and lower in the lenti-inhibitor group(P<0.05).Subcutaneous lung-cancer xenografts in the irradiation group and lenti-mir-30a-5p increased in size slowly;tumors were lighter and tumor inhibition rates were higher than those in the non-irradiation and lenti-GFP groups.In contrast,the opposite of these effects was observed in the lenti-inhibitor group.Immunohistochemistry and Western blotting indicated that ATM protein expression level was lower in the lenti-mir-30a-5p group,with or without irradiation,compared to that in the lenti-GFP group.ATM protein levels were higher in the lenti-inhibitor groups.The phosphorylation level of ATM at residue 1981 was low in the groups without irradiation and increased significantly after irradiation(P<0.05).Moreover,the phosphorylation level was lower in the lenti-mir-30a-5p group and higher in the lenti-inhibitor group than that in the lenti-GFP group after irradiation(P<0.05).Conclusion Mir-30a-5p enhanced the radiosensitivity of nude mice with subcutaneous lung-cancer xenografts by inhibiting ATM phosphorylation.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Foundationof China (11175222, 11205219), Western Talent Program of Chinese Academy of Sciences (Y460040XB0, Y160180XB0).
文摘Telomerase inhibitor MST-312 is a new compound derived from epigallocatechin gallate (EGCG)[1]. Our resultsdemonstrated that 4 M MST-312 not only showed lower cytotoxicity, but also inhibited telomerase activity inHepG2 cells. Therefore, in our experiments, 4 M MST-312 was chosen to study radiosensitization and relatedmechanisms. -H2AX foci are considered as an indicator of DNA damages[2]. The immunofluorescence stainingresults showed the number of -H2AX foci in the pretreatment with MST-312 followed by 2 Gy X-ray irradiationgroup. However, as shown in Fig. 1, the formation of Rad51 foci in the combined treatment group was blockedoutside the nuclear of HepG2 cells, when compared with the irradiation alone group. JC-1 staining showed thatMST-312 pretreatment, followed by X-ray irradiation, caused increase of the green/red fluorescence intensity ratio(ΔΨm) compared with X-ray irradiation alone. Meanwhile, MST-312 pretreatment followed by X-ray irradiationelevated expression of p53 protein and decreased expression of caspase-3 as well as fraction of Bcl-2 / Bax.
基金supported by the NIH(1R01DK103363)CPRIT(RP120588 and RP140544)the start-up fund from the University of Texas at Dallas.
文摘Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries,whether surface ligands can affect their radiosensitization has seldom been investi-gated in the radiosensitization of AuNPs.By conducting head-to-head comparison on radio-sensitization of two kinds of ultrasmall(~2 nm)near-infrared(NIR)emitting AuNPs that are coated with zwitterionic glutathione and neutr al polyethylene glyol(PEG)ligands,respectively,we found that zwitterionic glut athione coated AuNPs(GS-AuNPs)can reduce survival rates of MCF-7 cells under irr adiation of clinically used megavoltage photon beam at low dosage of~2.25 Gy.On the other hand,PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation,clearly indicating the key role of surface cheistry in radiosensitization of AuNPs.More detailed studies suggested that such difference was inde-pendent of cellular uptake and its eficiency,but might be related to the ligand-induced difference in photoelectron generation and/or inter actions between AuNPs and X-ray triggered reactive oxygen species(ROS).
基金supported by grants from the National Key R&D Program of China(Grant Nos.2018YFE0205100 and 2018YFE0205101)the National Natural Science Foundation of China(Grant Nos.11605260 and 31670859)+4 种基金the Key Research and Development Projects of Shanxi Province(Grant No.201903D321115)the Science and Technology Talent Project in Lanzhou(Grant No.2018-RC-66)the Science and Technology Project of Chengguan District of Lanzhou(Grant No.2020RCCX0038)the CAMS Innovation Fund for Medical Science(Grant No.2017-I2M-1-016)the Ministry of Education,Culture,Sports,and Science Technology Grantin-Aid for Scientific Research on Innovative Areas with Heavy Ions at NIRS-HIMAC,Japan[Grant Nos.JP15K21745,15H05944,and 15H05935(Living in Space),and Research Project Grant(14J313)].
文摘Objective:The aim of the present study was to investigate the mechanisms responsible for the radiation-sensitizing effect of antennapedia proteins,ANTP-SMACN7,on lung cancer cells treated with accelerated carbon and Fe particle irradiation.Methods:The ANTP-SMACN7 fusion peptide was synthesized and linked to fluorescein isothiocyanate to determine its ability to penetrate cells.A549 and NCI-H460 cells,human non-small cell lung cancer(NSCLC)cell lines,were irradiated with X-ray or high linear energy transfer(LET)irradiation with or without ANTP-SMACN7 treatment.Cellular survival,apoptosis,and protein expression were studied by colony formation assays,flow cytometry,and western blot analyses,respectively.Results:ANTP-SMACN7 fusion proteins entered the cells and promoted A549 and NCI-H460 cell high LET irradiation radiosensitization.High LET irradiation was more efficient for clonogenic cell killing and the induction of apoptosis(P<0.05).Treatment with ANTP-SMACN7 significantly reduced the A549 and NCI-H460 cell clone-forming percentages and increased apoptosis through inhibition of the X-linked inhibitor of apoptosis protein and the activation of caspase-3 and caspase-9.Conclusions:Regarding pharmaceutical radiosensitization,these findings provided a way to improve high-LET clinical radiotherapy for NSCLC patients.
基金supported by the Taishan Scholar Youth Expert Program in Shandong Province(Grant Number:tsqnz20230608)grants from the Natural Science Foundation of Shandong Province(Grant Number:ZR2023QB045)+1 种基金Scientific Research of Distinguished Professor from Qingdao University,China(Grant Numbers:DC2200000953,RZ2300002607,and RZ2400001462)grant from Natural Science Foundation of Qingdao Municipality,Shandong Province,China(Grant Number:23-2-1-30-zyyd-jch).
文摘Current radiotherapy(RT)lacks the ability to accurately discriminate between tumor and healthy tissues,resulting in significant radiation-induced damage for patients.Therefore,there is an urgent need for precise RT techniques that can optimize tumor control while minimizing adverse effects on surrounding healthy tissues.In this study,we developed a nanodrug(AuNR@Peptide)composed of furin-responsive RVRR peptide-conjugated AuNRs,which integrates an activatable probe and a radiosensitizer into a single system for accurate tumor localization,enabling imageguided precision RT.Upon reaching the tumor site after intravenous administration,proteolytic cleavage of RVRR substrates on AuNR@Peptide by biomarker triggers aggregation of gold nanorods(AuNRs)into larger aggregates,leading to activation of near-infrared(NIR)-II photoacoustic(PA)signals to precisely localize the tumor and enhance tumor retention by preventing migration and backflow of AuNRs.This significantly amplifies radiosensitivity efficiency.The peak time point at which the NIR-II PA signal was observed at the tumor site after injection serves as a reference for initiating RT,demonstrating substantial improvement in tumor RT through investigations related to radiosensitization mechanisms.The integration of imaging and therapy in this study offers a promising image-guided therapeutic modality for tumors.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39830090).
文摘Riboflavin, suggested to be a radiosensitizer, was studied in murine thymocytes and human hepatoma L02 cell line in vitro with MTT method and fluorescence microscopy. When the murine thymocytes treated with 5-400 μmol/L riboflavin were irradiated by 5 Gy 60Co γ ionizing radiation, the low concentration groups, i.e. treated with 5-50 μmol/L riboflavin, showed a different surviving fractions-time relating correlation compared with the high concentration groups, i.e. treated with 100-400 μmol/L riboflavin. The former had a high survival level at the end of irradiation, but which, after 4-h incubation, decreased rapidly to a low level. On the contrary, the high concentration groups showed a low survival level at the end of irradiation, and a poor correlation was found between the surviving fraction and the incubation time, after 4 h a little difference was observed. The results of fluorescence microscopy indicated that under low concentration conditions, the riboflavin localized mainly in nucleus (both perinuclear area and inside of nuclear membrane), while under high concentration conditions, intensive riboflavin also localized around cytoplasmic membranes. Thus we can conclude: the riboflavin had radiosensitivity effect on DNA under low concentration conditions, and enhanced the damage to cytoplasmic membrane under high concentration conditions. Also the most effective concentration of riboflavin can be evaluated to be approximate 100 μmol/L.
基金supported by the Project of Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region(grant number GZSY22-69)the Middle/Young aged Teachers’Research Ability Improvement Project of Guangxi Higher Education(grant number 2024KY0120).
文摘Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 and cell cloning experiments were applied to evaluate the effects of SPE on the proliferation of CNE-2R cells,and a single-hit multitarget model was used to calculate the radiobiological parameters.Cell apoptosis and cell cycle were analyzed by flow cytometry,and the levels of genes and proteins of the Raf/MEK/ERK pathway were determined by RT-PCR and Western blotting.Results:A total of 37 compounds from SPE were identified,and SPE with or without irradiation inhibited the proliferation of CNE-2R cells.SPE also promoted apoptosis,arrested cells in the G_(2)/M phase,and presented radiosensitizing effects.Compared with irradiation alone,the effects of SPE+irradiation on apoptosis and cell cycle distribution were not significantly different.In addition,SPE had no significant effect on MEK gene expression.SPE significantly increased the gene expression of C-Raf and significantly reduced the protein expression of C-Raf,as well as the gene and protein expression of ERK1 and ERK2.The protein levels of C-Raf,ERK1,and ERK2 were also significantly lower in cells treated with SPE+irradiation than in cells treated with irradiation alone.Conclusions:The effects of SPE on inhibiting cell proliferation and promoting apoptosis are likely associated with cell cycle arrest and Raf/MEK/ERK pathway regulation,and the mechanism underlying radiosensitization by SPE may involve downregulating the protein expression of C-Raf,ERK1,and ERK2.
文摘Colorectal cancer(CRC)remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages.Despite advancements in early screening and therapeutic interventions,the outcomes of patients with advanced-stage CRC remain suboptimal,as these patients continue to exhibit a persistently low 5-year survival rate.Palliative radiotherapy(RT)is crucial for advanced CRC patients,but radioresistance remains a significant clinical challenge.This resistance is attributed to multiple mechanisms,such as genetic heterogeneity,dysregulated DNA damage repair and tumor microenvironment metabolic disorders.Recent studies have shown that noncoding RNAs(ncRNAs),mainly microRNAs,long ncRNAs(lncRNAs)and circular RNAs,play pivotal roles in regulating CRC radiosensitivity through diverse mechanisms,such as epithelial-mesenchymal transition,epigenetic reprogramming,posttranscriptional regulation and oncogenic signaling pathway activation.For example,microRNAs such as miR-141-3p and miR-630 enhance CRC radiosensitivity by targeting oncogenic pathways.In addition,lncRNAs,including the lncRNAs HOTAIR and LINC00630,influence the radiosensitivity of CRC through interactions with the DNA damage repair machinery and epigenetic modulators,respectively.In addition,circ_0124554 acts as a competitive endogenous RNA to regulate oncogenic signaling.ncRNAs also serve as potential biomarkers for predicting radiosensitivity and prognosis.This review synthesizes the current evidence on the ncRNA-mediated regulatory networks that influence CRC radiosensitivity,emphasizing their potential as therapeutic targets to overcome RT resistance and improve outcomes in advanced CRC.By bridging mechanistic insights with clinical applications,this work aims to guide future research and the implementation of precision RT strategies.
基金Supported by the National Key R&D Program of China,No.2022YFC2503700 and No.2022YFC2503703the National Health Commission Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX005.
文摘BACKGROUND Esophageal cancer(ESCA)poses a significant challenge in oncology because of the limited treatment options and poor prognosis.Therefore,enhancing the therapeutic effects of radiotherapy for ESCA and identifying relevant therapeutic targets are crucial for improving both the survival rate and quality of life of patients.AIM To define the role of the transcription factor Snail family transcriptional repressor 1(SNAI1)in ESCA,particularly its regulation of radiosensitivity.METHODS A comprehensive analysis of TCGA data assessed SNAI1 expression in ESCA.Survival curves correlated SNAI1 levels with radiotherapy outcomes.Colony formation assays,flow cytometry,and a xenograft model were used to evaluate tumor radiosensitivity and apoptosis.Western blot validated protein expression,while Chromatin im-munoprecipitation assays examined SNAI1's role in regulating epithelial-mesenchymal transition(EMT).RESULTS SNAI1 expression in ESCA cell lines and clinical specimens emphasizes its central role in this disease.Elevated SNAI1 expression is correlated with unfavorable outcomes in radiotherapy.Downregulation of SNAI1 enhances the sensitivity of ESCA cells to ionizing radiation(IR),resulting in remarkable tumor regression upon IR treatment in vivo.This study underscores the direct involvement of SNAI1 in the regulation of EMT,particularly under IR-induced conditions.Furthermore,inhibiting deacetylation effectively suppresses EMT,suggesting a potential avenue to enhance the response to radiotherapy in ESCA.CONCLUSION This study highlights SNAI1's role in ESCA radiosensitivity,offering prognostic insights and therapeutic strategies to enhance radiotherapy by targeting SNAI1 and modulating EMT processes.
