铁死亡激活剂Erastin通过活化凋亡增强卵巢癌细胞顺铂敏感性的研究

Ferroptosis inducer Erastin enhances cisplatin sensitivity in human epithelial ovarian cancer cells by activating apoptosis

目的:探讨铁死亡激活剂Erastin对人上皮性卵巢癌细胞顺铂(DDP)敏感性的影响及其机制。方法:CCK-8法检测上皮性卵巢癌细胞株HEY、SKOV3、OVCAR3、ES2对Erastin的敏感性,选择Erastin不敏感的细胞株,CCK-8法测定联合Erastin前后顺铂半数抑制浓度(IC50),流式细胞学检测细胞凋亡,Western blot检测凋亡相关蛋白caspase 3的表达情况。结果:人上皮性卵巢癌HEY、SKOV3、OVCAR3、ES2细胞株中,HEY、SKOV3细胞株对Erastin引起的细胞死亡较不敏感。在联合Erastin后,细胞顺铂的IC50值显著降低(P<0.05)。流式结果提示Erastin可以增加顺铂诱导的HEY、SKOV3凋亡细胞数,Western blot结果显示促凋亡蛋白cleaved-caspase 3表达升高。结论:铁死亡激活剂Erastin可能通过活化凋亡通路进而提高HEY、SKOV3细胞对顺铂的敏感性。铁死亡激活剂可为改善临床EOC铂类耐药提供全新的思路。

Objective:To investigate the effects of ferroptosis inducer Erastin on regulating cisplatin sensitivity in human ovarian cancer cells.Methods:CCK-8 method was used to detect the sensitivity of epithelial ovarian cancer cell lines HEY,SKOV3,OVCAR3,and ES2 to Erastin.Cell lines less sensitive to Erastin were selected.CCK-8 method was used to determine the half cell lethal dose(IC50)of cisplatin with or without combination of Erastin.The ratios of apoptosis in EOC cells were determined by flow cytometry.Western blot was used to access the expression of apoptosis-related protein caspase 3.Results:HEY and SKOV3 were less sensitive to cell death caused by Erastin in these EOC cell lines.Erastin could significantly reduce the IC50 of cisplatin in HEY and SKOV3(P<0.05).Flow cytometry results showed that Erastin could increase apoptosis induced by cisplatin in HEY and SKOV3.Meanwhile the expression of pro-apoptotic protein cleaved-caspase 3 was increased(P<0.05).Conclusion:Ferroptosis inducer Erastin may increase the chemosensitivity to cisplatin by activating the apoptosis pathway in human epithelial ovarian cancer cell lines,which suggests that Erastin can provide a new perspective on the chemotherapy of human epithelial ovarian carcinoma.