| 金鹏程,林杰,朱鹏磊.二甲双胍诱导铁死亡抑制胶质瘤细胞增殖的机制研究[J].浙江中西医结合杂志,2023,33(2): |
| 二甲双胍诱导铁死亡抑制胶质瘤细胞增殖的机制研究 |
| Mechanism of metformin-induced ferroptosis inhibiting glioma cell proliferation JIN Pengcheng, LIN Jie, ZHU Penglei. Department of Neurosurgery, Wenzhou People’s Hospital, Wenzhou (325000), China |
| 投稿时间：2022-02-09 修订日期：2023-01-13 |
| DOI： |
| 中文关键词: 二甲双胍 胶质瘤 铁死亡 增殖 |
| 英文关键词:metformin glioma ferroptosis proliferation |
| 基金项目:温州市基础性医疗卫生科技项目(No. Y2020983) |
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| 中文摘要: |
| 目的 探讨二甲双胍通过诱导铁死亡抑制胶质瘤细胞增殖的作用和机制。方法 常规培养正常人神经胶质细胞和胶质瘤细胞,ELISA检测细胞脂质过氧化产物(5-、12- 和 15-HETE)的变化,免疫印迹检测细胞铁死亡标志蛋白GPX4和ACSL-4表达；二甲双胍处理胶质瘤细胞U87,CCK-8检测细胞活力改变,克隆形成实验检测细胞克隆形成能力,LDH试剂盒检测细胞LDH释放量,EdU染色检测细胞增殖,MDA试剂盒检测细胞MDA水平,流式细胞术检测细胞ROS水平,免疫印迹检测细胞铁死亡标志蛋白GPX4和ACSL-4蛋白表达；二甲双胍联合铁死亡抑制剂(ferrostatin-1)处理U87细胞,进一步验证胶质瘤细胞铁死亡机制。结果 与正常胶质细胞相比,胶质瘤细胞脂质过氧化产物5-、12- 和 15-HETE水平降低,铁死亡标志蛋白GPX4表达增多,ACSL-4蛋白表达减少,表明胶质瘤铁死亡减少；二甲双胍处理U87细胞后,铁死亡蛋白GPX4表达减少,ACSL-4蛋白表达增多,MDA 水平和ROS水平增加,细胞活力下降,表明二甲双胍促进胶质瘤铁死亡,抑制细胞增殖；铁死亡抑制剂ferrostatin-1联合二甲双胍处理U87细胞,GPX4 表达增多,ACSL-4 表达减少,MDA 和ROS水平降低,细胞活力升高,表明二甲双胍通过诱导胶质瘤铁死亡抑制细胞增殖。结论 二甲双胍通过促进胶质瘤细胞U87铁死亡的发生从而抑制细胞增殖。 |
| 英文摘要: |
| To investigate the effect and mechanism of metformin in inhibiting the proliferation of glioma cells by inducing ferroptosis. Methods Normal human glial cells and glioma cells were routinely cultured, the changes of lipid peroxidation products (5-, 12- and 15-HETE) were detected by ELISA, and the ferroptosis marker proteins GPX4 and ACSL-4 were detected by western blotting; Glioma cell U87 was treated with metformin, cell viability was detected by CCK-8, clone formation was detected by colony formation assay, LDH release was detected by LDH kit, cell proliferation was detected by EdU staining, and MDA level was detected by MDA kit , flow cytometry was used to detect the level of cellular ROS, and western blotting was used to detect the expression of ferroptosis marker proteins GPX4 and ACSL-4; U87 cells were treated with metformin combined with ferrostatin-1, which is the inhibitor of ferroptosis, to study the further mechanism. Results Compared with normal glial cells, the levels of lipid peroxidation products 5-, 12- and 15-HETE in glioma cells decreased, the expression of ferroptosis marker protein GPX4 increased, the expression of ACSL-4 protein decreased, indicating that glioma ferroptosis decreased; After metformin treatment of U87 cells, the expression of ferroptosis protein GPX4 decreased, the expression of ACSL-4 protein increased, the level of MDA and ROS increased, and the cell viability decreased, indicating that metformin promotes ferroptosis in gliomas and inhibits cell proliferation; U87 cells were treated with ferroptosis inhibitor (ferrostatin-1) combined with metformin, the expression of GPX4 increased, the expression of ACSL-4 decreased, the levels of MDA and ROS decreased, and the cell viability increased, indicating that metformin inhibits cell proliferation by inducing ferroptosis in gliomas. Conclusion Metformin inhibits cell proliferation by promoting ferroptosis in U87 glioma cells. |
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