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目的探讨二甲双胍(Met)增强子宫内膜癌顺铂(DDP)化疗敏感性及其可能机制。方法体外培养子宫内膜癌Ishikawa细胞,采用不同浓度的Met和DDP单药或联合用药处理。MTT检测各组细胞的增殖活性,流式细胞术检测两药单用及合用对Ishikawa细胞凋亡和周期的影响,Western blot法检测药物干预后子宫内膜癌细胞内胰岛素生长因子1(IGF-1)和雷帕霉素靶蛋白(mTOR)表达量的变化。结果 Met呈浓度和时间依赖性增强DDP对Ishikawa细胞增殖的抑制(P<0.05)。与Met或DDP单药组比较,联合用药组细胞的凋亡率高(P<0.05),Ishikawa细胞中G0/G1期细胞比例增加,S期细胞比例降低,IGF-1和mTOR蛋白表达水平下降(P<0.05)。结论 Met不仅能对子宫内膜癌细胞的增殖产生抑制作用,同时也可以增强DDP对子宫内膜癌化疗的敏感性,其作用机制可能与Met降低IGF-1和mTOR的表达有关。
Objective To investigate the sensitivity and possible mechanism of metformin (Met) in enhancing the chemotherapy of cisplatin (DDP) in patients with endometrial carcinoma. Methods Ishikawa cells were cultured in vitro and treated with different concentrations of Met and DDP alone or in combination. The proliferation of Ishikawa cells was detected by MTT assay. The apoptosis and cycle of Ishikawa cells were detected by flow cytometry (FCM). The levels of insulin-like growth factor-1 (IGF- 1) and rapamycin target protein (mTOR) expression changes. Results Met inhibited the proliferation of Ishikawa cells in a concentration-and time-dependent manner (P <0.05). Compared with Met or DDP group, the apoptosis rate of combination group was higher (P <0.05), the proportion of cells in G0 / G1 phase was increased, the proportion of cells in S phase was decreased, the expression of IGF-1 and mTOR protein was decreased in Ishikawa cells (P <0.05). Conclusion Met not only inhibits the proliferation of endometrial cancer cells, but also enhances the sensitivity of DDP to chemotherapy of endometrial cancer, which may be related to the decrease of IGF-1 and mTOR expression by Met.