第41卷第3期2023年6月广东医科大学学报JOURNALOFGUANGDONGMEDICALUNIVERSITYVol.41No.3Jun.2023266哌啶甲苯磺酰脒通过靶向GPX4基因调控人卵巢癌细胞铁死亡刘思溢,侯鉴基,招冠钰,孙阳,刘义,吴斌华*(广东医科大学海洋医药研究院,广东湛江524023)摘要:目的探讨哌啶甲苯磺酰脒(PMSA)对人卵巢癌细胞(SKOV3细胞)活力的影响,及其诱导细胞发生铁死亡的潜在分子机制。方法SKOV3细胞用不同浓度PMSA(0、2.5、5、10、20、40μmol/L)处理,分别用MTT、Annexin-V-FITC/PI染色、流式细胞术、Westernblot检测细胞活力、死亡、活性氧(ROS)、铁死亡相关信号通路分子表达。结果PMSA以浓度依赖性方式抑制SKOV3细胞活性,增加细胞死亡及ROS含量,减少GPX4和p-Nrf2表达(P<0.01或0.05)。分子对接预测PMSA与GPX4蛋白直接结合。结论PMSA通过靶向GPX4诱导SKOV3细胞铁死亡,从而发挥抗癌作用。关键词:卵巢癌;哌啶甲苯磺酰脒;铁死亡中图分类号:R737文献标志码:A文章编号:2096-3610(2023)03-0266-064-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamideregulatesferroptosisofhumanovariancancercellsthroughGPX4geneLIUSi-yi,HOUJian-ji,ZHAOGuan-yu,SUNYang,LIUYi,WUBin-hua*(MarineBiomedicalResearchInstitute,GuangdongMedicalUniversity,Zhanjiang524023,China)Abstract:ObjectiveTostudytheeffectof4-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamide(PMSA)onactivityandferroptosisofhumanovariancancercelllineSKOV3.MethodsAftertreatedwithdifferentconcentrations(0,2.5,5,10,20,40μmol/L)ofPMSA,viability,death,reactiveoxygenspecies(ROS),andferroptosis-relatedsignalingmoleculesofSKOV3cellsweredetectedbyMTT,AnnexinV-FITC/PIstaining,flowcytometry,andWesternblot,respectively.ResultsPMSAdose-dependentlyinhibitedtheviability,increasedthedeathandROScontent,anddecreasedtheexpressionofGPX4andphosphorylatedNrf2inSKOV3cells(P<0.01or0.05).MoleculardockingresultsindicatedthatPMSAcoulddirectlybindtoGPX4.ConclusionPMSAmightplayananti-cancerrolebyGPX4-targetedinductionofferroptosisinSKOV3cells.Keywords:ovariancancer;PMSA;ferroptosis卵巢癌是一种具有较高发病率和病死率的女性生殖系统癌症[1]。由于传统的治疗方法存在治疗周期长、副作用大等缺陷,近年来人们正在深入探究更新、更有效的治...