目的 探究α-常春藤皂苷对卵巢癌A2780细胞铁死亡的影响及其作用机制。方法 A2780细胞给予α-常春藤皂苷处理，采用CCK8法检测细胞活力；试剂盒分别检测细胞内Fe²⁺、谷胱甘肽（GSH）、丙二醛（MDA）及细胞内总活性氧（ROS）水平；Western blotting法检测铁死亡蛋白表达；CCK8法检测铁死亡抑制剂检测对细胞活力的恢复作用。结果 α-常春藤皂苷处理A2780细胞24 h，细胞存活率随着浓度的增加显著下降，IC₅₀值为19.92 µmol/L。与对照组相比，A2780细胞的体外克隆形成随着α-常春藤皂苷浓度的升高明显减少（P＜0.01）。10 μmol/L Fer-1处理的A2780细胞能显著减少α-常春藤皂苷对A2780细胞的抑制作用（P＜0.01）。与对照组相比，α-常春藤皂苷各浓度组细胞的GSH水平明显降低，α-常春藤皂苷20、30 μmol/L组Fe²⁺水平及α-常春藤皂苷30 μmol/L组MDA水平显著升高（P＜0.05、0.01）。与对照组相比，α-常春藤皂苷30 μmol/L组细胞内ROS荧光强度显著增加（P＜0.01）。与对照组相比，α-常春藤皂苷30 μmol/L组细胞内溶质载体家族7成员11（SLC7A11）、谷胱甘肽过氧化酶4（GPX4）蛋白表达显著降低（P＜0.05、0.01）。α-常春藤皂苷各浓度组SLC7A11、GPX4 mRNA表达均显著降低。（P＜0.01）。结论 α-常春藤皂苷可以抑制卵巢癌A2780细胞的增殖，并通过抑制SLC7A11、GPX4的表达来诱导铁死亡，进而发挥抗卵巢癌的作用。

Objective To investigate the effect of α-hederin on ferroptosis of ovarian cancer A2780 cells and its mechanism. Methods A2780 cells were treated with α-hederin, and the cell viability was detected by CCK8 method. The levels of intracellular Fe²⁺, GSH, MDA, and total ROS were detected by kits. The expression of ferroptosis-related protein was detected by Western blotting. The effect of ferroptosis inhibitor on the recovery of cell function was detected. Results After treating A2780 cells with α-hederin for 24 hours, the cell survival rate significantly decreased with the increase of concentration, and the IC₅₀ value was 19.92 μmol/L. Compared with control group, the in vitro colony formation of A2780 cells decreased significantly with the increase of α-hederin concentration (P < 0.01). The A2780 cells treated with 10 μmol/L Fer-1 could significantly reduce the inhibitory effect of α-hederin on A2780 cells (P < 0.01). Compared with control group, the GSH levels in cells of each concentration group of α-hederin were significantly decreased, while the Fe²⁺ levels in the α-hederin 20 and 30 μmol/L groups, and the MDA levels in the α-hederin 30 μmol/L group were significantly increased (P < 0.05, 0.01). Compared with the control group, the fluorescence intensity of ROS in cells of the α-hederin 30 μmol/L group was significantly increased (P < 0.01). Compared with the control group, the protein expression of SLC7A11 and GPX4 in cells of the α-hederin 30 μmol/L group was significantly decreased (P < 0.05, 0.01). The mRNA expression of SLC7A11 and GPX4 in each concentration group of α-hederin was significantly decreased (P < 0.01). Conclusion α-Hederin can inhibit the proliferation of A2780 cells and induce ferroptosis by inhibiting the expression of SLC7A11 and GPX4, thereby exerting an anti-ovarian cancer effect.

R287.4

国家自然科学基金面上项目(82072088)