GPX4介导铁死亡在上皮性卵巢癌顺铂耐药细胞中的作用  

Role of the mechanism of GPX4-mediated ferroptosis in cisplatin-resistant epithelial ovarian cancer cells

作　　者：葛树杰 胡永全[1] 周晓静 袁超[1] GE Shujie;HU Yongquan;ZHOU Xiaojing;YUAN Chao(The First Affiliated Hospital of Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]蚌埠医学院第一附属医院,安徽蚌埠233030

出　　处：《华夏医学》2023年第4期42-46,共5页Acta Medicinae Sinica

基　　金：蚌埠医学院自然科学类项目(2021byzd141);2019年度蚌埠市科技创新指导类项目(201940)。

摘　　要：目的:探讨谷胱甘肽过氧化酶4(GPX4)介导铁死亡在上皮性卵巢癌顺铂耐药细胞中的作用。方法:以CCK8技术检测SKOV3细胞转染pcDNA3.l-GPX4及pcDNA3.l-NC后在不同浓度DDP中的药物耐受性(IC50);对SKOV3/DDP细胞分别进行RSL3(2μg/ml)、RSL3(2μg/ml)+DDP(5μg/ml)和RSL3(2μg/ml)+DDP(5μg/ml)+Fer-l(lμmol/L)处理,以蛋白质印记技术检测相关蛋白表达变化;对SKOV3/DDP细胞转染pcDNA3.l-GPX4及pcDNA3.l-NC后分别进行RSL3(2μg/ml)+DDP(5μg/ml)和RSL3(2μg/ml)+DDP(5μg/ml)+Fer-l(lμmol/L)处理,测量荧光强度。结果:SKOV3(GPX4)细胞对DDP的IC50明显增高。分别进行RSL3和RSL3+DDP处理的SKOV3/DDP细胞中的xCT和GPX4下降;给Fer-l与DDP、RSL3同时处理时,SKOV3/DDP细胞中的xCT和GPX4逆转上升;与SKOV3/DDP(阴性对照)细胞相比,SKOV3/DDP(GPX4)细胞中的RSL3+DDP组和Fer-l+RSL3+DDP组荧光强度降低,以上组间比较均有统计学差异(P<0.05)。在SKOV3/DDP(阴性对照)和SKOV3/DDP(GPX4)细胞中,Fer-l+RSL3+DDP组与RSL3+DDP组的荧光强度均降低(P<0.05)。结论:GPX4可以提高SKOV3细胞对于DDP的耐受性,且在上皮性卵巢癌顺铂耐药细胞中可以靶向抑制铁死亡。Objective:To explore the role of the mechanism of glutathione peroxidase 4(GPX4)mediated ferroptosis in cisplatin-resistant epithelial ovarian cancer cells.Methods:The CCK8 technique was used to detect drug tolerance(IC50)of SKOV3 cells transfected with pcDNA3.l-GPX4 or pcDNA3.l-NC at different concentrations of DDP;SKOV3/DDP cells were treated with RSL3(2μg/ml),RSL3(2μg/ml)+DDP(5μg/ml),and RSL3(2μg/ml)+DDP(5μg/ml)+Fer-l(1μmol/L).Changes in relevant protein expression were detected using protein imprinting technology;SKOV3/DDP cells were transfected with pcDNA3.l-GPX4 or pcDNA3.l-NC and treated with RSL3(2μg/ml)+DDP(5μg/ml)or RSL3(2μg/ml)+DDP(5μg/ml)+Fer-l(1μmol/L),and fluorescence intensity was measured.Results:The IC50 of SKOV3(GPX4)cells to DDP was significantly increased.The expression of xCT and GPX4 in SKOV3/DDP cells treated with RSL3 and RSL3+DDP decreased;when Fer-l was treated simultaneously with DDP and RSL3,the expression of xCT and GPX4 in SKOV3/DDP cells increased.Compared with SKOV3/DDP(negative control)cells,the fluorescence intensity of the RSL3+DDP and Fer-l+RSL3+DDP groups in SKOV3/DDP(GPX4)cells decreased,and the difference was statistically significant between the groups(P<0.05).In both SKOV3/DDP(negative control)and SKOV3/DDP(GPX4)cells,the fluorescence intensity decreased in the Fer-l+RSL3+DDP group compared to the RSL3+DDP group(P<0.05).Conclusion:GPX4 can enhance the tolerance of SKOV3 cells to DDP,target and inhibit ferroptosis in platinum-resistant epithelial ovarian cancer cells.

关 键 词：谷胱甘肽过氧化酶4 铁死亡 上皮性卵巢癌 顺铂 耐药细胞 

分 类 号：R737.31[医药卫生—肿瘤]