OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METH...OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METHODS:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 groups.Tripterygium wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control group.Three days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal saline.Rat joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving therapy.Myocardial ultrastructure was observed by electron microscope.Enzyme-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial tissue.Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and Smad7.Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.RESULTS:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more marked.Consistently,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate,dihydroxyacetone phosphate,arachidonic acid,etc was defined and implicated in amino acid,glucose,and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.CONCLUSION:Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions.The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.展开更多
OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)trea...OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)treated with platelet-derived growth factor(PDGF)-BB to establish a asthma model in vivo and in vitro.The cell morphology was observed with microscope and immunofluorescence staining.The cell viability was assessed with methyl thiazolyl tetrazolium assay.The tumor necrosis factor-αlpha(TNF-α),interleukin-1beta(IL-1β),laminin,fibronectin and collagen IV levels in the ASMCs were detected with corresponding enzyme linked immunosorbent assay kits.Transwell and wound healing assays were conducted to test the cell migration.The TGF-β1,Smad2 and Smad3 levels were measured with Western blot.RESULTS:We found that QFJJ formula treatment dramatically decreased the cell viability,TNF-α,IL-1β,laminin,fibronectin and collagen IV levels in the PDGFBB stimulated ASMCs.Additionally,the protein levels of TGF-β1,Smad2 and Smad3 in the PDGF-BB stimulated ASMCs were prominently depleted after QFJJ formula treatment.Besides,SRI treatment neutralized the role of QFJJ formula in the PDGF-BB stimulated ASMCs.CONCLUSION:QFJJ formula effectively relieved the asthma progression through ameliorate the ASMCs function,which was achieved through suppressing the TGF-β1/Smads signaling pathway.展开更多
目的对比转化生长因子β1(TGF-β1)、Smad2、Smad3以及上皮间质转化(epithelial mesenchymal transition,EMT)相关标志物在不同类型慢性鼻窦炎(CRS)患者中的表达特征,分析E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(vim...目的对比转化生长因子β1(TGF-β1)、Smad2、Smad3以及上皮间质转化(epithelial mesenchymal transition,EMT)相关标志物在不同类型慢性鼻窦炎(CRS)患者中的表达特征,分析E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(vimentin)在不同类型CRS患者中与TGF-β1及手术治疗预后的相关性。方法使用蛋白免疫印迹法和实时荧光定量聚合酶链反应对比不同类型CRS患者和对照组中E-cadherin、N-cadherin、vimentin、TGF-β1、Smad2和Smad3的表达,分析其与术后各临床评分改善程度的相关性。结果与对照组相比,CRSsNP组、non-ECRSwNP组和ECRSwN P组中E-cad her i n表达下降,vimenti n、N-cad her i n表达上升。TGF-β1在CRSsN P组中的蛋白表达高于non-ECRSwNP组和对照组(P均<0.001),Smad2和Smad3在CRSsNP组中的表达高于ECRSwNP组、non-ECRSwNP组和对照组(P均<0.001)。在CRSsNP组中,TGF-β1与vimentin之间有正相关关系(r=0.675,P=0.011),与E-cadherin有负相关关系(r=-0.802,P=0.001)。E-cadherin表达与不同类型CRS患者SNOT-22鼻部症状评分改善幅度均呈负相关关系(P均<0.05)。结论不同类型CRS中均发生EMT现象,在CRSsNP中EMT可能与TGF-β1/Smad信号通路有关。EMT标志物的表达与CRS患者术后疾病严重程度的下降幅度有相关性,提示EMT过程与CRS患者手术预后潜在的关联性。展开更多
Objectives:Ovarian cancer(OC)is a highly heterogeneous disease characterized by high metastatic potential and frequent recurrence.3β-hydroxysterolΔ24-reductase(DHCR24)is closely associated with the progression of va...Objectives:Ovarian cancer(OC)is a highly heterogeneous disease characterized by high metastatic potential and frequent recurrence.3β-hydroxysterolΔ24-reductase(DHCR24)is closely associated with the progression of various malignant tumors,but its role in OC remains unexplored.This study is the first to systematically investigate the function of DHCR24 in OC and elucidate its mechanism in promoting OC progression,providing novel theoretical insights for targeted therapy.Methods:The expression of DHCR24 was evaluated in tissues using bioinformatics and clinical data;the impact of DHCR24 on the malignant behavior of OC was assessed through in vivo and in vitro experiments;and the mechanism by which DHCR24 functions in OC was preliminarily explored using sequencing and rescue experiments.Statistical analysis was conducted using the chi-square test,t-test,and oneway ANOVA.Results:Database,clinical data,and immunohistochemical(IHC)analyses demonstrated that DHCR24 is upregulated in OC and correlates with poor outcomes.In vitro experiments indicated that DHCR24 promotes proliferation,migration,invasion,and epithelial-mesenchymal transition in OC cells.The addition of a DHCR24 inhibitor suppressed the malignant behavior of OC cells.The nude mouse tumor formation experiment demonstrated that inhibiting DHCR24 suppresses the in vivo growth of OC cells.Further experiments showed that DHCR24 promotes the malignant behavior of OC cells,correlating with the regulation of the transforming growth factor beta(TGF-β)signaling pathway.All the above experiments showed statistical significance.Conclusion:DHCR24 contributes to ovarian cancer progression by upregulating the TGF-β1 pathway,highlighting its potential as a therapeutic target in ovarian cancer.展开更多
OBJECTIVE:To investigate the mechanism by which Sini decoction(四逆汤,SND)improves renal fibrosis(Rf)in rats based on transforming growth factor β1/Smad(TGF-β1/Smad)signaling pathway.METHODS:Network pharmacology was...OBJECTIVE:To investigate the mechanism by which Sini decoction(四逆汤,SND)improves renal fibrosis(Rf)in rats based on transforming growth factor β1/Smad(TGF-β1/Smad)signaling pathway.METHODS:Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf.The targets of SND drug components and the targets of Rf were obtained by searching databases,such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP)and GeenCard.The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram.Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway.The Rf rat model was established by unilateral ureteral occlusion(UUO).The expression levels of transforming growth factor,matrix metalloproteinase-9(MMP-9),matrix metal protease-2(MMP-2),connective tissue growth factor(CTGF),and tissue inhibitor of metalloproteinase-1(TIMP-1)were determined by Masson staining of rat renal tissue,and immunohistochemical methods.The expression levels of Smad3,Smad2,and Smad7 in renal tissue were determined by Western blotting(WB).The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway.RESULTS:A total of 12 drug components of Fuzi(Radix Aconiti Lateralis Preparata),5 drug components of Ganjiang(Rhizoma Zingiber),and 9 drug components of Gancao(Radix Glycy et Rhizoma)were obtained from the database search,and 207 shared targets were found.A total of 1063 Rf targets were found in the database search.According to the Venn diagram,in total,96 intersection targets were found in two database searches.The metabolic pathways involved included TGF-β signaling pathway,phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling(PI3K/Akt)pathway,and hypoxia-inducible factor-1(HIF-1)signaling pathway.Masson staining analysis showed that compared with the model group,the renal interstitial collagen deposition levels in the SSN and SND groups were significantly lower(P<0.05).Immunohistochemical analysis,compared with the control group,the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the model group were significantly decreased(P<0.05,P<0.01),and the positive cell area expression levels of CTGF and TGF-β1 were significantly increased(P<0.01).Compared with the model group,the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the SSN and SND groups were significantly increased(P<0.05,P<0.01),and the positive cell area expression levels of CTGF and TGF-β1 in the kidney tissue were significantly decreased(P<0.05,P<0.01).WB results showed that the SSN group and the SND group could reduce the expression of Smad2 and Smad3(P<0.05)and increase the expression of Smad7(P<0.05).展开更多
OBJECTIVE:To examine the influence of SaponinⅠfrom Shuitianqi(Rhizoma Schizocapasae Plantagineae)(SSPHⅠ)on hepatocellular carcinoma(HCC)metastasis,and to elucidate the underlying mechanism.METHODS:The intrahepatic m...OBJECTIVE:To examine the influence of SaponinⅠfrom Shuitianqi(Rhizoma Schizocapasae Plantagineae)(SSPHⅠ)on hepatocellular carcinoma(HCC)metastasis,and to elucidate the underlying mechanism.METHODS:The intrahepatic metastasis Bagg's Albino/c(BALB/c)mouse model was established with human hepatocellular carcinomas(HepG2)cells,then treated with normal saline(once per day),cisplatin(2 mg/kg,once every 2 d),and SSPHⅠ(25,50,and 75 mg/kg,once per day).Then,we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology techniques.RESULTS:Based on our analysis,SSPHⅠsignificantly alleviated hepatocyte necrosis and tumor cells infiltration.Moreover,SSPHⅠsuppressed extracellular matrix(ECM)degradation and angiogenesis via a decrease in matrix etalloproteinase-2(MMP-2),MMP-9,CD31,CD34,and vascular endothelial growth factor(VEGF)levels.Furthermore,SSPHⅠrepressed invasion and metastasis by suppressing the transforming growth factor-β1(TGF-β1)/Smad7 axis and epithelial-mesenchymal transition(EMT),as evidenced by the scarce TGF-β1,Ncadherin,and Vimentin expressions,and elevated Smad7 and E-cadherin expressions.CONCLUSION:The SSPHⅠ-mediated negative regulation of the TGF-β1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.展开更多
基金National Natural Science Foundation of China:a Metabolomic Study of the Effects of Moxibustion on Cardiac Function and Its Intervention in RA Model Rats Based on the TGF-β1/Smads Signaling Pathway (No.81403484)Anhui Province University Natural Science Fund Project of China:Exploring the Mechanism of Action of Moxibustion in AA Rats Based on Intestinal Flora and TLR4/NF-KB Signaling Pathway (No.KJ2019A0448)+2 种基金National Project Cultivation Fund Project Plan:Exploring the Mechanism of Action of Moxibustion in AA Rats Based on Intestinal Flora and TLR4/NF-KB Signaling Pathway (No.2019py01)Anhui Province Clinical Medical Research Center [Anhui Provincial Science and Technology Department Anhui Social Science (2020) No.41]the training Program of Outstanding talents in Colleges and Universities:2021 Domestic Visiting Training Program for Outstanding Young Key Teachers in Colleges and Universities (No.gxgnfx2021122)
文摘OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling pathway.METHODS:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 groups.Tripterygium wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control group.Three days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal saline.Rat joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving therapy.Myocardial ultrastructure was observed by electron microscope.Enzyme-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial tissue.Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and Smad7.Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer.RESULTS:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more marked.Consistently,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate,dihydroxyacetone phosphate,arachidonic acid,etc was defined and implicated in amino acid,glucose,and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis.CONCLUSION:Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions.The protective effects might be associated with its role in TGF-β1 inactivation and metabolic reprogramming.
基金Supported by Science and Technology Innovation Project of China Academy of Chinese Medical Sciences of Study on the Mechanism of Qufeng Jiejing Formula in Regulating Mitogen-activated Protein Kinase Signaling Pathway to Inhibit Phenotypic Transformation of Airway Smooth Muscle Cells in Asthma(No.CI2021A01108)Cultivation Project of The National Natural Science Foundation of China of Xiyuan Hospital,China Academy of Chinese Medical Sciences of Research on the Role of Traditional Chinese Medicines-Qufeng Jiejing in the Proliferation,Migration and Phenotypic Transformation of Airway Smooth Muscle Cells in Asthma(No.XY20-17)。
文摘OBJECTIVE:To explore the role and mechanism of Qufeng Jiejing(祛风解痉,QFJJ)formula in the asthma progression.METHODS:The Bagg Albino/c mice treated with Ovalbumin and AL(OH)3,and airway smooth muscle cells(ASMCs)treated with platelet-derived growth factor(PDGF)-BB to establish a asthma model in vivo and in vitro.The cell morphology was observed with microscope and immunofluorescence staining.The cell viability was assessed with methyl thiazolyl tetrazolium assay.The tumor necrosis factor-αlpha(TNF-α),interleukin-1beta(IL-1β),laminin,fibronectin and collagen IV levels in the ASMCs were detected with corresponding enzyme linked immunosorbent assay kits.Transwell and wound healing assays were conducted to test the cell migration.The TGF-β1,Smad2 and Smad3 levels were measured with Western blot.RESULTS:We found that QFJJ formula treatment dramatically decreased the cell viability,TNF-α,IL-1β,laminin,fibronectin and collagen IV levels in the PDGFBB stimulated ASMCs.Additionally,the protein levels of TGF-β1,Smad2 and Smad3 in the PDGF-BB stimulated ASMCs were prominently depleted after QFJJ formula treatment.Besides,SRI treatment neutralized the role of QFJJ formula in the PDGF-BB stimulated ASMCs.CONCLUSION:QFJJ formula effectively relieved the asthma progression through ameliorate the ASMCs function,which was achieved through suppressing the TGF-β1/Smads signaling pathway.
文摘目的对比转化生长因子β1(TGF-β1)、Smad2、Smad3以及上皮间质转化(epithelial mesenchymal transition,EMT)相关标志物在不同类型慢性鼻窦炎(CRS)患者中的表达特征,分析E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(vimentin)在不同类型CRS患者中与TGF-β1及手术治疗预后的相关性。方法使用蛋白免疫印迹法和实时荧光定量聚合酶链反应对比不同类型CRS患者和对照组中E-cadherin、N-cadherin、vimentin、TGF-β1、Smad2和Smad3的表达,分析其与术后各临床评分改善程度的相关性。结果与对照组相比,CRSsNP组、non-ECRSwNP组和ECRSwN P组中E-cad her i n表达下降,vimenti n、N-cad her i n表达上升。TGF-β1在CRSsN P组中的蛋白表达高于non-ECRSwNP组和对照组(P均<0.001),Smad2和Smad3在CRSsNP组中的表达高于ECRSwNP组、non-ECRSwNP组和对照组(P均<0.001)。在CRSsNP组中,TGF-β1与vimentin之间有正相关关系(r=0.675,P=0.011),与E-cadherin有负相关关系(r=-0.802,P=0.001)。E-cadherin表达与不同类型CRS患者SNOT-22鼻部症状评分改善幅度均呈负相关关系(P均<0.05)。结论不同类型CRS中均发生EMT现象,在CRSsNP中EMT可能与TGF-β1/Smad信号通路有关。EMT标志物的表达与CRS患者术后疾病严重程度的下降幅度有相关性,提示EMT过程与CRS患者手术预后潜在的关联性。
文摘Objectives:Ovarian cancer(OC)is a highly heterogeneous disease characterized by high metastatic potential and frequent recurrence.3β-hydroxysterolΔ24-reductase(DHCR24)is closely associated with the progression of various malignant tumors,but its role in OC remains unexplored.This study is the first to systematically investigate the function of DHCR24 in OC and elucidate its mechanism in promoting OC progression,providing novel theoretical insights for targeted therapy.Methods:The expression of DHCR24 was evaluated in tissues using bioinformatics and clinical data;the impact of DHCR24 on the malignant behavior of OC was assessed through in vivo and in vitro experiments;and the mechanism by which DHCR24 functions in OC was preliminarily explored using sequencing and rescue experiments.Statistical analysis was conducted using the chi-square test,t-test,and oneway ANOVA.Results:Database,clinical data,and immunohistochemical(IHC)analyses demonstrated that DHCR24 is upregulated in OC and correlates with poor outcomes.In vitro experiments indicated that DHCR24 promotes proliferation,migration,invasion,and epithelial-mesenchymal transition in OC cells.The addition of a DHCR24 inhibitor suppressed the malignant behavior of OC cells.The nude mouse tumor formation experiment demonstrated that inhibiting DHCR24 suppresses the in vivo growth of OC cells.Further experiments showed that DHCR24 promotes the malignant behavior of OC cells,correlating with the regulation of the transforming growth factor beta(TGF-β)signaling pathway.All the above experiments showed statistical significance.Conclusion:DHCR24 contributes to ovarian cancer progression by upregulating the TGF-β1 pathway,highlighting its potential as a therapeutic target in ovarian cancer.
基金National Natural Science Foundation of China:General Program:Research on the Protective Effect of Component Wu Sini Decoction on Hypothyroidism and Kidney Injury and Its Mechanism of Action(No.81373546)Study on the Protective Effect and Mechanism of Wu Sini decoction on Renal Fibrosis(No.2016021165)+1 种基金Shanxi University of Chinese Medicine Pharmacology Discipline Construction Project(No.2023XKJS-25)Shanxi University of Chinese Medicine Pharmacy Discipline Construction Project(No.2023XKJS-26)。
文摘OBJECTIVE:To investigate the mechanism by which Sini decoction(四逆汤,SND)improves renal fibrosis(Rf)in rats based on transforming growth factor β1/Smad(TGF-β1/Smad)signaling pathway.METHODS:Network pharmacology was applied to obtain potentially involved signaling pathways in SND's improving effects on Rf.The targets of SND drug components and the targets of Rf were obtained by searching databases,such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP)and GeenCard.The intersection targets of two searches were obtained and underwent signaling pathway analysis using a Venn diagram.Then experimental pharmacology was utilized to prove and investigate the effects of SND on target proteins in the TGF-β1/Smad signaling pathway.The Rf rat model was established by unilateral ureteral occlusion(UUO).The expression levels of transforming growth factor,matrix metalloproteinase-9(MMP-9),matrix metal protease-2(MMP-2),connective tissue growth factor(CTGF),and tissue inhibitor of metalloproteinase-1(TIMP-1)were determined by Masson staining of rat renal tissue,and immunohistochemical methods.The expression levels of Smad3,Smad2,and Smad7 in renal tissue were determined by Western blotting(WB).The mechanism of the improving effects of SND on Rf was investigated based on TGF-β1/Smad signaling pathway.RESULTS:A total of 12 drug components of Fuzi(Radix Aconiti Lateralis Preparata),5 drug components of Ganjiang(Rhizoma Zingiber),and 9 drug components of Gancao(Radix Glycy et Rhizoma)were obtained from the database search,and 207 shared targets were found.A total of 1063 Rf targets were found in the database search.According to the Venn diagram,in total,96 intersection targets were found in two database searches.The metabolic pathways involved included TGF-β signaling pathway,phosphatidylinositol-3-kinase/serine-threonine protein kinase signaling(PI3K/Akt)pathway,and hypoxia-inducible factor-1(HIF-1)signaling pathway.Masson staining analysis showed that compared with the model group,the renal interstitial collagen deposition levels in the SSN and SND groups were significantly lower(P<0.05).Immunohistochemical analysis,compared with the control group,the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the model group were significantly decreased(P<0.05,P<0.01),and the positive cell area expression levels of CTGF and TGF-β1 were significantly increased(P<0.01).Compared with the model group,the positive cell area expression levels of MMP-9/TIMP-1 and MMP-2/TIMP-1 in the kidney tissue of the SSN and SND groups were significantly increased(P<0.05,P<0.01),and the positive cell area expression levels of CTGF and TGF-β1 in the kidney tissue were significantly decreased(P<0.05,P<0.01).WB results showed that the SSN group and the SND group could reduce the expression of Smad2 and Smad3(P<0.05)and increase the expression of Smad7(P<0.05).
基金National Natural Science Foundation of China,a New Anti-cancer Plant drug,SaponinⅠfrom Shuitianqi(Rhizoma Schizocapasae Plantagineae),against Invasion and Metastasis of Non-small Cell Lung Cancer and Reversing Tyrosine Kinase Inhibitors Resistance basing on Human Growth Factor/c-Mesenchymal to Epithelial Transition Factor Pathway and its Molecular Mechanism of Regulating Epithelial-Mesenchymal Transition(No.8164062)the Natural Science Foundation of Guangxi Province,Study on the Antihepatic Fibrosis Mechanism of Saponins from Shuitianqi(Rhizoma Schizocapasae Plantagineae)based on Transforming Growth Factor-β/Smad Signaling Pathway(No.2019GXNSFAA245075)。
文摘OBJECTIVE:To examine the influence of SaponinⅠfrom Shuitianqi(Rhizoma Schizocapasae Plantagineae)(SSPHⅠ)on hepatocellular carcinoma(HCC)metastasis,and to elucidate the underlying mechanism.METHODS:The intrahepatic metastasis Bagg's Albino/c(BALB/c)mouse model was established with human hepatocellular carcinomas(HepG2)cells,then treated with normal saline(once per day),cisplatin(2 mg/kg,once every 2 d),and SSPHⅠ(25,50,and 75 mg/kg,once per day).Then,we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology techniques.RESULTS:Based on our analysis,SSPHⅠsignificantly alleviated hepatocyte necrosis and tumor cells infiltration.Moreover,SSPHⅠsuppressed extracellular matrix(ECM)degradation and angiogenesis via a decrease in matrix etalloproteinase-2(MMP-2),MMP-9,CD31,CD34,and vascular endothelial growth factor(VEGF)levels.Furthermore,SSPHⅠrepressed invasion and metastasis by suppressing the transforming growth factor-β1(TGF-β1)/Smad7 axis and epithelial-mesenchymal transition(EMT),as evidenced by the scarce TGF-β1,Ncadherin,and Vimentin expressions,and elevated Smad7 and E-cadherin expressions.CONCLUSION:The SSPHⅠ-mediated negative regulation of the TGF-β1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.
