二甲双胍对LKB1基因过表达的子宫内膜癌HEC-1A细胞的影响

目的 研究二甲双胍对LKB1基因过表达的子宫内膜癌HEC-1A细胞的增殖与细胞周期的影响。方法 以不同浓度的二甲双胍作用于LKB1基因过表达的子宫内膜癌HEC-1A细胞（LKB组）与缺失LKB1基因表达的HEC-1A细胞（CON组）。用流式细胞术仪检测各组HEC-1A细胞的细胞周期；RT-PCR法和Western blot技术检测各组HEC-1A细胞的LKB1、mTOR基因与蛋白的表达；以平板克隆法与细胞迁移实验检测各组细胞的细胞增殖水平。结果 与缺失LKB1基因表达的HEC-1A细胞比较，LKB1基因过表达的HEC-1A细胞随着二甲双胍浓度的升高明显降低细胞克隆形成率、细胞迁移率、S 期细胞比例及mTOR基因与蛋白的表达，而增加G₀ /G₁期细胞比例及LKB1基因与蛋白的表达，差异均有统计学意义（P均<0.05）。结论 二甲双胍抑制LKB1基因过表达的子宫内膜癌HEC-1A细胞的生长和侵袭，其机制可能为介导LKB1/mTOR信号传导通路而抑制子宫内膜癌细胞的增殖。

Effect of metformin on HEC-1A endometrial cancer cells in the presence of LKB1 overex-pression

Objective To investigate the effect of metformin on proliferation and cell cycle of HEC-1A endometrial cancer cells in the presence of LKB1 overexpression. Methods HEC-1A cells overexpressing LKB1 and control HEC-1A cells were treated with different concentrations of metformin. The two groups were compared in terms of proliferation rate，cell migration ability and cell cycle using a colony formation assay，transwell experiments and flow cytometry. Expression of LKB1 and mTOR mRNA was measured using RT-PCR，and levels of the corresponding proteins were measured using Western blotting. Results Treating LKB1-overexpressing HEC-1A cells with metformin inhibited colony formation，cell motility，and expression of mTOR mRNA and protein in a dose-dependent manner relative to control HEC-1A cells（P<0.05）. It also reduced the proportion of LKB1-overexpressing HEC-1A cells in S phase relative to controls（P<0.05）. Conversely，treating LKB1-overexpressing HEC-1A cells with metformin increased the proportion of cells in G₀ /G₁ phase and upregulated expression of LKB1 mRNA and protein in a dose-dependent manner（P<0.05）. Conclusion Metformin inhibits proliferation and cell migration of HEC-1A endometrial cancer cells overexpressing LKB1，potentially by acting on the LKB1/mTOR signaling pathway.