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

4-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamide regulates ferroptosis of human ovarian cancer cells through GPX4 gene

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、AnnexinV-FITC/PI染色、流式细胞术、Western blot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。

Objective To study the effect of 4-methyl-N-(piperidin-1-ylmethylene)benzenesulfonamide(PMSA)on activity and ferroptosis of human ovarian cancer cell line SKOV3.Methods After treated with different concentrations(0,2.5,5,10,20,40μmol/L)of PMSA,viability,death,reactive oxygen species(ROS),and ferroptosis-related signaling molecules of SKOV3 cells were detected by MTT,Annexin V-FITC/PI staining,flow cytometry,and Western blot,respectively.Results PMSA dose-dependently inhibited the viability,increased the death and ROS content,and decreased the expression of GPX4 and phosphorylated Nrf2 in SKOV3 cells(P<0.01 or 0.05).Molecular docking results indicated that PMSA could directly bind to GPX4.Conclusion PMSA might play an anti-cancer role by GPX4-targeted induction of ferroptosis in SKOV3 cells.