中国比较医学杂志2026，Vol.36Issue(1)：34-42,9.DOI:10.3969/j.issn.1671-7856.2026.01.004
沉默GTSE1通过Hippo-YAP/TAZ通路调控上皮间质转化对卵巢癌卡铂耐药的影响
Silencing GTSE1 regulates epithelial-mesenchymal transition via the Hippo-YAP/TAZ pathway to influence carboplatin resistance in ovarian cancer
摘要
Abstract
Objective To elucidate the role of G2/S phase expressed 1(GTSE1)in carboplatin resistance mechanisms in ovarian cancer.Methods(1)GTSE1 protein expression was compared between carboplatin-sensitive(OVCAR3,OV3R-CBP,COC1)cell lines by Western blot.(2)GTSE1 was then silenced in OV3R-CBP cells using small interfering(si)RNA transfection si-GTSE1 or si-normal control(NC),and the knockdown efficiency was confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot.Carboplatin dose-response assays(0,10,20,40,80 and 160 μmol/L)were conducted to determine the half-maximal inhibitory concentration(IC50)and drug resistance index.(3)OV3R-CBP cells were treated with various combinations:carboplatin alone(70 μmol/L,CBP group),carboplatin plus LY2109761(10 μmol/L,CBP+si+LY2109261 group),carboplatin plus si-NC(CBP+si-NC group),carboplatin plus si-GTSE1(CBP+si-GTSE1 group),and a triple combination of carboplatin,si-GTSE1 and XMU-MP-1(1 μmol/L,CBP+si-GTSE1+XMU-MP-1 group).Expression levels of E-cadherin,Vimentin,Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)were detected by Western blot.Cell proliferation inhibition and apoptosis were assessed by Cell Counting Kit-8 assay and flow cytometry.Results(1)GTSE1 expression was significantly elevated in OV3R-CBP relative to OVCAR3/COC1 cells(P<0.05).(2)Knockdown of GTSE1 significantly decreased GTSE1 mRNA/protein levels and carboplatin IC50 and resistance index(P<0.05).(3)Silencing GTSE1 in the presence of carboplatin suppressed YAP,TAZ,and Vimentin expression,and enhanced E-cadherin expression,YAP/TAZ phosphorylation,cell proliferation inhibition,and apoptosis(P<0.05).Hippo pathway inhibition using XMU-MP-1 reversed these effects,indicating pathway-specific modulation.Conclusions Silencing GTSE1 reverses carboplatin resistance in ovarian cancer cells by activating the Hippo-YAP/TAZ pathway and inhibiting epithelial-mesenchymal transition.Targeting GTSE1 restores chemosensitivity via reactivation of the Hippo pathway,offering a potential therapeutic strategy for overcoming platinum resistance in ovarian cancer.关键词
卵巢癌/GTSE1/YAP/TAZ/上皮间质转化/卡铂/耐药Key words
ovarian cancer/GTSE1/YAP/TAZ/epithelial-mesenchymal transition/carboplatin/resistance分类
医药卫生引用本文复制引用
李娅茹,孙丽妍,宋永祯,林萍,陈欢..沉默GTSE1通过Hippo-YAP/TAZ通路调控上皮间质转化对卵巢癌卡铂耐药的影响[J].中国比较医学杂志,2026,36(1):34-42,9.基金项目
河北省医学科学研究课题计划项目(20211492). （20211492）
