二甲双胍对LKB1基因过表达的子宫内膜癌HEC-1A细胞的影响  

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

作　　者：宋玥[1,2] 宋红林[1] 唐乔乔[2] 潘月琼 何君葵 赵瑞奇[2] 

机构地区：[1]广西医科大学附属肿瘤医院妇瘤二科,南宁530021 [2]广西医科大学研究生学院,南宁530021

出　　处：《中国癌症防治杂志》2015年第1期12-17,共6页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：广西自然科学基金资助项目(2011GXNSFA018253)

摘　　要：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、m TOR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m TOR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/m TOR信号传导通路而抑制子宫内膜癌细胞的增殖。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 m TOR m RNA was measured using RTPCR,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 m TOR m RNA and protein in a dose-dependent manner relative to control HEC-1A cells（P0.05）. It also reduced the proportion of LKB1-overexpressing HEC-1A cells in S phase relative to controls（P0.05）. Conversely,treating LKB1 overexpressing HEC-1A cells with metformin increased the proportion of cells in G0/G1 phase and upregulated expression of LKB1 m RNA and protein in a dose-dependent manner（P0.05）. Conclusion Metformin inhibits proliferation and cell migration of HEC-1A endometrial cancer cells overexpressing LKB1,potentially by acting on the LKB1/m TOR signaling pathway.

关 键 词：子宫肿瘤 肝激酶基因 HEC-1A细胞 二甲双胍 胰岛素抵抗 

分 类 号：R737.33[医药卫生—肿瘤]