Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
We investigated the expression of transient receptor potential canonical 6 （TRPC6） protein in benign and malignant human prostate tissues and in prostate cancer cell lines and the association with the stage, grade a...We investigated the expression of transient receptor potential canonical 6 （TRPC6） protein in benign and malignant human prostate tissues and in prostate cancer cell lines and the association with the stage, grade and androgen responsiveness of the tumors. Immunohistochemical techniques, Western blot and reverse transcription polymerase chain reaction （RT-PCR） were used to investigate TRPC6 expression. TRPC6 protein was detected in 9 of 20 （45.0%） of benign prostatic hyperplasia （BPH） cases, and there was a significant difference compared with prostate cancer （129 of 149 [86.6%]） （P 〈 0.01）. TRPC6 expression was associated with the histological grade and extraprostatic extension （P 〈 0.01）. Tumors of higher stage tended to have a higher frequency of TRPC6 protein staining, but the difference was not significant among T2, T3 and T4. TRPC6 expression difference between androgen-independent （AI） tumors and androgen-dependent （AD） tumors was not statistically significant. TRPC6 was also observed in prostate cancer cell lines. In summary, TRPC6 is detected in benign and malignant human prostate tissues and prostate cancer cell lines and is associated with the histological grade, Gleason score and extraprostatic extension of prostate cancer.展开更多
The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called g...The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.展开更多
Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkyl...Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkylating agents, diminish multidrug resistance and decrease metastasis. Whether or not it can induce autophagy in cancer cells has not yet been determined. Here we investigated the antiproliferative activity of apogossypolone （ApoG2） and （-）-gossypol on the human prostate cancer cell line PC3 and LNCaP in vitro. Exposure of PC-3 and LNCaP cells to ApoG2 resulted in several specific features characteristic of autophagy, including the appearance of membranous vacuoles in the cytoplasm and formation of acidic vesicular organelles. Expression of autophagy-associated LC3-Ⅱ and beclin-1 increased in both cell lines after treatment. Inhibition of autophagy with 3-methyladenine promoted apoptosis of both cell types. Taken together, these data demonstrated that induction of autophagy could represent a defense mechanism against apoptosis in human prostate cancer cells.展开更多
The specificity of prostate-specific antigen （PSA） for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 （PCA3） may be more accurate in outcome prediction than other methods for the ...The specificity of prostate-specific antigen （PSA） for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 （PCA3） may be more accurate in outcome prediction than other methods for the early detection of prostate cancer （PCa）. However, the results were inconsistent in repeated biopsies. Therefore, we performed a systematic review and meta-analysis to evaluate the role of PCA3 in outcome prediction. A systematic bibliographic search was conducted for articles published before April 2013, using PubMed, Medline, Web of Science, Embase and other databases from health technology assessment agencies. The quality of the studies was assessed on the basis of QUADAS criteria. Eleven studies of diagnostic tests with moderate to high quality were selected. A meta-analysis was carried out to synthesize the results. The results of the meta-analyses were heterogeneous among studies. We performed a subgroup analysis （with or without inclusion of high-grade prostatic intraepithelial neoplasia （HGPIN） and atypical small acinar proliferation （ASAP））. Using a PCA3 cutoff of 20 or 35, in the two sub-groups, the global sensitivity values were 0.93 or 0.80 and 0.79 or 0.75, specificities were 0.65 or 0.44 and 0.78 or 0.70, positive likelihood ratios were 1.86 or 1.58 and 2.49 or 1.78, negative likelihood ratios were 0.81 or 0.43 and 0.91 or 0.82 and diagnostic odd ratios （ORs） were 5.73 or 3.45 and 7.13 or 4.11, respectively. The areas under the curve （AUCs） of the summary receiver operating characteristic curve were 0.85 or 0.72 and 0.81 or 0.69, respectively. PCA3 can be used for repeat biopsy of the prostate to improve accuracy of PCa detection. Unnecessary biopsies can be avoided by using a PCa cutoff score of 20.展开更多
Objective:To study the expression of TRPC6 among prostate cancer cells,establish high expression cell lines of TRPC6,and to provide potential cell mode for prostate cancer oncogenesis and development.Methods:Occurrenc...Objective:To study the expression of TRPC6 among prostate cancer cells,establish high expression cell lines of TRPC6,and to provide potential cell mode for prostate cancer oncogenesis and development.Methods:Occurrence and development of prostate cancer cells,PC3,PC—3m DU145,22 rvl,LNCaP and normal prostate epithelial cells in the PrEC TRPC6 expression level were detected by QPCR method.Calcium phosphate transfection method was used to package retrovirus pLEGFP-Nl-TRPC6 and pLEGFP-Nl-vector and infect the prostate cancer cells,a stable high expression of TRPC6 prostate cancer cells.Sable cell lines of TRPC6,matrix metalloproteinase(MMP)2,MMP9 expression was detected by QPCR and Western blot.Change of cell invasion ability was detected by Transwell.Results:The expression level of prostate cancer cells TRPC6 were higher than control group PrEC cells.Among TPRC6 the expression of cell line PC 3 transfer potential wre the lowest,and high transfer cell tone PC-3M express was the highest.Real-time fluorescent quantitative PCR and western blot results showed that after filter,the seventh generation of cell TRPC6 protein and mRNA expression levels were higher than the control group obviously.Transwell experimental results showed that the overexpression of TRPC6could promote the invasion ability of PC.3 prostate cancer cells.Conclusions:TRPC6 expressed in prostate cancer cells is in disorder,and its action may be associated with the invasion and metastasis of prostate cancer cells;successful establishment of stable high expression of TRPC6prostate cancer cells primarily confirm the invasion-trigger ability of TRPC6 on prostate cancer,and lay down the foundation for exploring the TRPC6's role in the occurrence and development of prostate cancer展开更多
Hepatocyte growth factor （HGF） is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 （TRPC6） channels is considered i...Hepatocyte growth factor （HGF） is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 （TRPC6） channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques （whole-cell patch clamp configuration） and Ca^2＋ imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-Iike currents evoked by oleoyl-2-acetyl-sn-glycerol （OAG）. Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG- and HGF-induced Ca^2＋ entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G2/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.展开更多
Prostate cancer gene 3 （PCA3, also known as DD3） is a new biomarker that could improve the accuracy of prostate cancer diagnosis. It is a great biomarker with fairly high specificity and sensitivity. The incidence o...Prostate cancer gene 3 （PCA3, also known as DD3） is a new biomarker that could improve the accuracy of prostate cancer diagnosis. It is a great biomarker with fairly high specificity and sensitivity. The incidence of prostate cancer is rising steadily in most countries. The commonly used prostate-specific antigen （PSA） test once gave people hope for early diagnosis of prostate cancer. However, the low specificity of the PSA test has resulted in a large number of unnecessary biopsies and overtreatment. During the past decade, many new prostate cancer biomarkers have been found. Among these, PCA3 is the most promising. Due to its great performance in distinguishing prostate cancer from other prostate conditions, PCA3 could likely be applied for early diagnosis of prostate cancer, patient follow-up, prognosis prediction, and targeted therapy. After years of research, we have obtained some knowledge about the sequence of PCA3 gene. We have also determined the relationship between PCA3 and the proliferation of prostate cancer cells and learned some information about how PCA3 affects tumor-related genes and proteins. A PCA3 score has been created, and it has been used in a variety of studies. Some researchers have even applied PCA3 to targeted therapy and obtained a good effect in vitro. This review describes the current state of research, and explores the future prospects for PCA3.展开更多
Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expres...Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expressing PC-3（AR）9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3（AR）2 （stable clone that expresses AR under the control of the cytomegalovirus （CMV） promoter, established by Heisler et al.） after androgen treatment. Results： We found that dihydrotestosterone （DHT） from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3（AR）2 compared with its vector control, PC-3（plRES）. In contrast, PC-3（AR）9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion： These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer （AIPC） PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3（AR）9 prostate cancer cells.展开更多
Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m ce...Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.展开更多
Aim： To evaluate the antiproliferative activity of contragestazol （DL111-IT） on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods： The cell k...Aim： To evaluate the antiproliferative activity of contragestazol （DL111-IT） on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods： The cell killing ability of DL111-IT was measured by the 3-（4,5-dimethylthia-zol,2-yl）-2,5-diphenyltetrazolium bromide （MTT） reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma （pRb）, cyclin-dependent kinase 4 （CDK4） and cyclin D 1, was detected by Western blotting. Results： DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50 % cell inhibition （IC50 value） was 9.9 mg/mL. In the PC3 tumor xenograft study, DL111-IT （1.25 mg/kg-20.0 mg/kg） given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50 %. Flow cytometric analysis indicated that DL111-IT could cause GI arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D 1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL 111- IT. Conclusion： DL111-1T inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.展开更多
We investigated the antiproliferative activity of （-）-gossypol on the human prostate cancer cell line PC3 in vitro and in vivo to elucidate its potential molecular mechanisms. Cell growth and viability were evaluate...We investigated the antiproliferative activity of （-）-gossypol on the human prostate cancer cell line PC3 in vitro and in vivo to elucidate its potential molecular mechanisms. Cell growth and viability were evaluated using the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and cell apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling （TUNEL） and electron microscopy. Expression of proliferating cell nuclear antigen （PCNA）, Bcl-2, CD31, caspase-3 and caspase-8 in tumour tissue was determined by immunohistochemistry. The drug concentration that yielded 50% cell inhibition （IC50 value） was 4.74 μg mL-1. In the PC-3 tumour xenograft study, （-）-gossypol （〉 5 mg kg-1） given once a day for 7 days significantly inhibited tumour growth in a dose-dependent manner. Immunohistochemical analysis revealed that （-）-gossypol enhanced caspase-3 and caspase-8 expression and decreased the expression of PCNA, Bcl-2 and CD31 in tumour tissues. It suggested that cell apoptosis and inhibition of angiogenesis might contribute to the anticancer action of （-）-gossypol.展开更多
Reduced microRNA （miRNA） let-7a expression and the activation of insulin-like growth factor-1 receptor （IGFIR） signalling are both involved in prostate cancer and progression. In the present study, we demonstrated...Reduced microRNA （miRNA） let-7a expression and the activation of insulin-like growth factor-1 receptor （IGFIR） signalling are both involved in prostate cancer and progression. In the present study, we demonstrated that the growth inhibitory effect of let-7al is directly related to targeting IGFIRgene expression in PC-3 cells. TargetScan predicted three potential target sites （T1, T2 and T3） of let-7a in the 3＇ untranslational region （3＇ UTR） of IGFIR mRNA. Real-time PCR, Western blot and luciferase reporter assays were used to detect the effects of let-7al overexpression or let-7al inhibitor on the IGFIRgene expression in PC-3 cells. The results indicated that let-7al could inhibit IGFIR expression by directly targeting the T1 and T2 sites in the 3＇ UTR of the IGFIR mRNA. We then used RT-PCR, luciferase reporter assays, 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） assay, flow cytometry and Hoechst 33342 staining to examine whether let-7al-mediated inhibition of IGFIR expression also affects the IGFIR-mediated signalling events, including Elk1 activity and c-fos gene expression, proliferation, apoptosis and cell cycle. We demonstrated that let-7al-mediated IGFIR downregulation was accompanied by attenuation of Elk1 activity and c-fos expression, inhibition of cell proliferation, enhanced apoptosis and cell cycle arrest, and that loss function of let-7al via inhibition can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. Altogether, these findings sueeest that let-7a mav be novel therapeutic candidate for Drostate cancer.展开更多
The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viabili...The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry. Cell proliferation ability was detected by colony formation assay. Cellular apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining, Hoechst 33258 fluorescent staining, and flow cytometry （FCM） with annexin Ⅴ-FITC/propidium iodide dual staining. The results showed that dracorhodin perchlorate inhibited the growth of PC-3 in a dose- and time-dependent manner. IC50 of dracorhodin perchlorate on PC-3 cells at 24 h was 40.18 μmol/L. Cell clone formation rate was decreased by 86% after treatment with 20 μmol/L of dracorhodin perchlorate. Some cells presented the characteristic apoptotic changes. The cellular apoptotic rates induced by 10-40 μmol/L dracorhodin perchlorate for 24 h were 8.43% to 47.71% respectively. It was concluded that dracorhodin perchlorate significantly inhibited the growth of PC-3 cells by suppressing proliferation and inducing apoptosis of the cells.展开更多
The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells wer...The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of mye- loid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated antiapoptotic proteins in androgen-independent prostate cancer cells in vitro.展开更多
Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with near...Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.展开更多
This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory p...This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.展开更多
Objective:To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells.Methods:Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetr...Objective:To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells.Methods:Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.Apoptosis and mitochondrial membrane potential(MMP)were measured using flow cytometry in PC3 cells.DNA damage was assessed by nuclear staining and DNA fragmentation assay.Expressions of apoptosis-associated proteins were determined by Western blotting assays.Activities of caspase-3,-8,and-9 were determined by colorimetric assay.Moreover,intracellular reactive oxygen species(ROS)generation was detected using a flow cytometer and fluorescence microscope.Results:Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation,which was associated with induction of apoptosis,and accompanied by increased expression of Fas,Fas-ligand(Fas L),Bax and t Bid,and decreased expression of Bcl-2.In addition,ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8,-9 and-3,resulting in an increase in poly(ADP-ribose)polymerase(PARP)cleavage.However,in the presence of a pan-caspase inhibitor,ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated.Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP,leading to cytosolic release of cytochrome c.Moreover,the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme,which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine.Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP,activation of caspase-3,the cytosolic release of cytochrome c and cytotoxicity.Conclusions:Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis.Therefore,ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.展开更多
Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathway...Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.展开更多
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
文摘We investigated the expression of transient receptor potential canonical 6 （TRPC6） protein in benign and malignant human prostate tissues and in prostate cancer cell lines and the association with the stage, grade and androgen responsiveness of the tumors. Immunohistochemical techniques, Western blot and reverse transcription polymerase chain reaction （RT-PCR） were used to investigate TRPC6 expression. TRPC6 protein was detected in 9 of 20 （45.0%） of benign prostatic hyperplasia （BPH） cases, and there was a significant difference compared with prostate cancer （129 of 149 [86.6%]） （P 〈 0.01）. TRPC6 expression was associated with the histological grade and extraprostatic extension （P 〈 0.01）. Tumors of higher stage tended to have a higher frequency of TRPC6 protein staining, but the difference was not significant among T2, T3 and T4. TRPC6 expression difference between androgen-independent （AI） tumors and androgen-dependent （AD） tumors was not statistically significant. TRPC6 was also observed in prostate cancer cell lines. In summary, TRPC6 is detected in benign and malignant human prostate tissues and prostate cancer cell lines and is associated with the histological grade, Gleason score and extraprostatic extension of prostate cancer.
基金supported by the following grants: National Natural Science Foundation of China No. 31571413, 31201037 (to Dr. Yu) and No. 81570180, 81072103 (to Dr. Wang) from the National Natural Science Foundation of China
文摘The incidence of prostate cancer （PCa） is rising steadily among males in many countries. Serum prostate-specific antigen （PSA） is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA （ncRNA） that is highly expressed in prostate cancer （PCa） cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PC43 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.
基金Acknowledgement This study was supported in part by the National Nature Science Foundation of China （No. 30772658, No. 30710403089 and No. 30970712）.
文摘Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkylating agents, diminish multidrug resistance and decrease metastasis. Whether or not it can induce autophagy in cancer cells has not yet been determined. Here we investigated the antiproliferative activity of apogossypolone （ApoG2） and （-）-gossypol on the human prostate cancer cell line PC3 and LNCaP in vitro. Exposure of PC-3 and LNCaP cells to ApoG2 resulted in several specific features characteristic of autophagy, including the appearance of membranous vacuoles in the cytoplasm and formation of acidic vesicular organelles. Expression of autophagy-associated LC3-Ⅱ and beclin-1 increased in both cell lines after treatment. Inhibition of autophagy with 3-methyladenine promoted apoptosis of both cell types. Taken together, these data demonstrated that induction of autophagy could represent a defense mechanism against apoptosis in human prostate cancer cells.
文摘The specificity of prostate-specific antigen （PSA） for early intervention in repeat biopsy is unsatisfactory. Prostate cancer antigen 3 （PCA3） may be more accurate in outcome prediction than other methods for the early detection of prostate cancer （PCa）. However, the results were inconsistent in repeated biopsies. Therefore, we performed a systematic review and meta-analysis to evaluate the role of PCA3 in outcome prediction. A systematic bibliographic search was conducted for articles published before April 2013, using PubMed, Medline, Web of Science, Embase and other databases from health technology assessment agencies. The quality of the studies was assessed on the basis of QUADAS criteria. Eleven studies of diagnostic tests with moderate to high quality were selected. A meta-analysis was carried out to synthesize the results. The results of the meta-analyses were heterogeneous among studies. We performed a subgroup analysis （with or without inclusion of high-grade prostatic intraepithelial neoplasia （HGPIN） and atypical small acinar proliferation （ASAP））. Using a PCA3 cutoff of 20 or 35, in the two sub-groups, the global sensitivity values were 0.93 or 0.80 and 0.79 or 0.75, specificities were 0.65 or 0.44 and 0.78 or 0.70, positive likelihood ratios were 1.86 or 1.58 and 2.49 or 1.78, negative likelihood ratios were 0.81 or 0.43 and 0.91 or 0.82 and diagnostic odd ratios （ORs） were 5.73 or 3.45 and 7.13 or 4.11, respectively. The areas under the curve （AUCs） of the summary receiver operating characteristic curve were 0.85 or 0.72 and 0.81 or 0.69, respectively. PCA3 can be used for repeat biopsy of the prostate to improve accuracy of PCa detection. Unnecessary biopsies can be avoided by using a PCa cutoff score of 20.
基金supported by Sichuan Province Department of Health(Grant Project:130188)
文摘Objective:To study the expression of TRPC6 among prostate cancer cells,establish high expression cell lines of TRPC6,and to provide potential cell mode for prostate cancer oncogenesis and development.Methods:Occurrence and development of prostate cancer cells,PC3,PC—3m DU145,22 rvl,LNCaP and normal prostate epithelial cells in the PrEC TRPC6 expression level were detected by QPCR method.Calcium phosphate transfection method was used to package retrovirus pLEGFP-Nl-TRPC6 and pLEGFP-Nl-vector and infect the prostate cancer cells,a stable high expression of TRPC6 prostate cancer cells.Sable cell lines of TRPC6,matrix metalloproteinase(MMP)2,MMP9 expression was detected by QPCR and Western blot.Change of cell invasion ability was detected by Transwell.Results:The expression level of prostate cancer cells TRPC6 were higher than control group PrEC cells.Among TPRC6 the expression of cell line PC 3 transfer potential wre the lowest,and high transfer cell tone PC-3M express was the highest.Real-time fluorescent quantitative PCR and western blot results showed that after filter,the seventh generation of cell TRPC6 protein and mRNA expression levels were higher than the control group obviously.Transwell experimental results showed that the overexpression of TRPC6could promote the invasion ability of PC.3 prostate cancer cells.Conclusions:TRPC6 expressed in prostate cancer cells is in disorder,and its action may be associated with the invasion and metastasis of prostate cancer cells;successful establishment of stable high expression of TRPC6prostate cancer cells primarily confirm the invasion-trigger ability of TRPC6 on prostate cancer,and lay down the foundation for exploring the TRPC6's role in the occurrence and development of prostate cancer
文摘Hepatocyte growth factor （HGF） is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 （TRPC6） channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques （whole-cell patch clamp configuration） and Ca^2＋ imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-Iike currents evoked by oleoyl-2-acetyl-sn-glycerol （OAG）. Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG- and HGF-induced Ca^2＋ entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G2/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.
基金supported by grants from the National Natural Science Foundation of China (81272836)
文摘Prostate cancer gene 3 （PCA3, also known as DD3） is a new biomarker that could improve the accuracy of prostate cancer diagnosis. It is a great biomarker with fairly high specificity and sensitivity. The incidence of prostate cancer is rising steadily in most countries. The commonly used prostate-specific antigen （PSA） test once gave people hope for early diagnosis of prostate cancer. However, the low specificity of the PSA test has resulted in a large number of unnecessary biopsies and overtreatment. During the past decade, many new prostate cancer biomarkers have been found. Among these, PCA3 is the most promising. Due to its great performance in distinguishing prostate cancer from other prostate conditions, PCA3 could likely be applied for early diagnosis of prostate cancer, patient follow-up, prognosis prediction, and targeted therapy. After years of research, we have obtained some knowledge about the sequence of PCA3 gene. We have also determined the relationship between PCA3 and the proliferation of prostate cancer cells and learned some information about how PCA3 affects tumor-related genes and proteins. A PCA3 score has been created, and it has been used in a variety of studies. Some researchers have even applied PCA3 to targeted therapy and obtained a good effect in vitro. This review describes the current state of research, and explores the future prospects for PCA3.
文摘Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expressing PC-3（AR）9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3（AR）2 （stable clone that expresses AR under the control of the cytomegalovirus （CMV） promoter, established by Heisler et al.） after androgen treatment. Results： We found that dihydrotestosterone （DHT） from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3（AR）2 compared with its vector control, PC-3（plRES）. In contrast, PC-3（AR）9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion： These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer （AIPC） PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3（AR）9 prostate cancer cells.
文摘Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.
基金This study received financial support from the National Natural Science Foundation of China(No.30000209).
文摘Aim： To evaluate the antiproliferative activity of contragestazol （DL111-IT） on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods： The cell killing ability of DL111-IT was measured by the 3-（4,5-dimethylthia-zol,2-yl）-2,5-diphenyltetrazolium bromide （MTT） reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma （pRb）, cyclin-dependent kinase 4 （CDK4） and cyclin D 1, was detected by Western blotting. Results： DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50 % cell inhibition （IC50 value） was 9.9 mg/mL. In the PC3 tumor xenograft study, DL111-IT （1.25 mg/kg-20.0 mg/kg） given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50 %. Flow cytometric analysis indicated that DL111-IT could cause GI arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D 1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL 111- IT. Conclusion： DL111-1T inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.
基金This study was supported in part by grants from National Natural Science Foundation of China （No. 30570494 and No. 30772658）. We thank Dr Xing- Bin Hu （The Second Department of Blood Transfusion, Xijing Hospital, Xi＇an, China） for assisting writing this manuscript.
文摘We investigated the antiproliferative activity of （-）-gossypol on the human prostate cancer cell line PC3 in vitro and in vivo to elucidate its potential molecular mechanisms. Cell growth and viability were evaluated using the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, and cell apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling （TUNEL） and electron microscopy. Expression of proliferating cell nuclear antigen （PCNA）, Bcl-2, CD31, caspase-3 and caspase-8 in tumour tissue was determined by immunohistochemistry. The drug concentration that yielded 50% cell inhibition （IC50 value） was 4.74 μg mL-1. In the PC-3 tumour xenograft study, （-）-gossypol （〉 5 mg kg-1） given once a day for 7 days significantly inhibited tumour growth in a dose-dependent manner. Immunohistochemical analysis revealed that （-）-gossypol enhanced caspase-3 and caspase-8 expression and decreased the expression of PCNA, Bcl-2 and CD31 in tumour tissues. It suggested that cell apoptosis and inhibition of angiogenesis might contribute to the anticancer action of （-）-gossypol.
基金This study was supported by grants from the National Natural Science Foundation of China （Nos. 81071720 and 81172045）, Shandong Provincial Programs for Science and Technology Development （No. 2012GSF 11820） and Foundation for Outstanding Young Scientist in Shandong Province （No. 2006BS03066）.
文摘Reduced microRNA （miRNA） let-7a expression and the activation of insulin-like growth factor-1 receptor （IGFIR） signalling are both involved in prostate cancer and progression. In the present study, we demonstrated that the growth inhibitory effect of let-7al is directly related to targeting IGFIRgene expression in PC-3 cells. TargetScan predicted three potential target sites （T1, T2 and T3） of let-7a in the 3＇ untranslational region （3＇ UTR） of IGFIR mRNA. Real-time PCR, Western blot and luciferase reporter assays were used to detect the effects of let-7al overexpression or let-7al inhibitor on the IGFIRgene expression in PC-3 cells. The results indicated that let-7al could inhibit IGFIR expression by directly targeting the T1 and T2 sites in the 3＇ UTR of the IGFIR mRNA. We then used RT-PCR, luciferase reporter assays, 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） assay, flow cytometry and Hoechst 33342 staining to examine whether let-7al-mediated inhibition of IGFIR expression also affects the IGFIR-mediated signalling events, including Elk1 activity and c-fos gene expression, proliferation, apoptosis and cell cycle. We demonstrated that let-7al-mediated IGFIR downregulation was accompanied by attenuation of Elk1 activity and c-fos expression, inhibition of cell proliferation, enhanced apoptosis and cell cycle arrest, and that loss function of let-7al via inhibition can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos expression, thereby enhancing cell proliferation. Altogether, these findings sueeest that let-7a mav be novel therapeutic candidate for Drostate cancer.
基金supported by a grant from the Key Project of Science and Technology of Wuhan (No. 201060938361-08)
文摘The growth inhibition and pro-apoptosis effects of dracorhodin perchlorate on human prostate cancer PC-3 cell line were examined. After administration of 10-80 μmol/L dracorhodin perchlorate for 12-48 h, cell viability of PC-3 cells was measured by MTT colorimetry. Cell proliferation ability was detected by colony formation assay. Cellular apoptosis was inspected by acridine orange-ethidium bromide fluorescent staining, Hoechst 33258 fluorescent staining, and flow cytometry （FCM） with annexin Ⅴ-FITC/propidium iodide dual staining. The results showed that dracorhodin perchlorate inhibited the growth of PC-3 in a dose- and time-dependent manner. IC50 of dracorhodin perchlorate on PC-3 cells at 24 h was 40.18 μmol/L. Cell clone formation rate was decreased by 86% after treatment with 20 μmol/L of dracorhodin perchlorate. Some cells presented the characteristic apoptotic changes. The cellular apoptotic rates induced by 10-40 μmol/L dracorhodin perchlorate for 24 h were 8.43% to 47.71% respectively. It was concluded that dracorhodin perchlorate significantly inhibited the growth of PC-3 cells by suppressing proliferation and inducing apoptosis of the cells.
基金We thank Mr Wen-Tong Meng and Mr Ji-Long Gou （Stem Cell Research Laboratory, West China Hospital, Sichuan University, Chengdu, China） for technical assistance with the flow cytometry. We also thank BioMed Proofreading for their editing work. This work was supported by grants to Prof. Hao Zeng and Dr Rui Huang from the National Natural Science Foundation of China （NSFC 30700977 and 30600153）.
文摘The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent can- cer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of mye- loid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated antiapoptotic proteins in androgen-independent prostate cancer cells in vitro.
文摘Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.
基金supported by grants from the National Natural Science Foundation of China(No.81373342)the Nature Science Foundation of Beijing(No.2141004)
文摘This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
基金a part of the project titled‘Omics based on fishery disease control technology development and industrialization(20150242)’‘Development of functional food products with natural materials derived from marine resources(2017-0377)’funded by the Ministry of Oceans and Fisheries,Republic of Korea.
文摘Objective:To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells.Methods:Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.Apoptosis and mitochondrial membrane potential(MMP)were measured using flow cytometry in PC3 cells.DNA damage was assessed by nuclear staining and DNA fragmentation assay.Expressions of apoptosis-associated proteins were determined by Western blotting assays.Activities of caspase-3,-8,and-9 were determined by colorimetric assay.Moreover,intracellular reactive oxygen species(ROS)generation was detected using a flow cytometer and fluorescence microscope.Results:Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation,which was associated with induction of apoptosis,and accompanied by increased expression of Fas,Fas-ligand(Fas L),Bax and t Bid,and decreased expression of Bcl-2.In addition,ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8,-9 and-3,resulting in an increase in poly(ADP-ribose)polymerase(PARP)cleavage.However,in the presence of a pan-caspase inhibitor,ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated.Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP,leading to cytosolic release of cytochrome c.Moreover,the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme,which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine.Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP,activation of caspase-3,the cytosolic release of cytochrome c and cytotoxicity.Conclusions:Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis.Therefore,ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.
基金financially supported by the Fundamental Research Grant Scheme,(FRGS/1/2016/SKK08/MUSM/02/1)under the Ministry of Higher Education,Malaysia
文摘Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one(MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17.Methods: PC-3 and DU145 cells were treated with 3 × EC_(50)(15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry.Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified.Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17.Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis.However, the expressions of CH60 and HS71 A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells.Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly.Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.
