二甲双胍在体外对人子宫内膜癌细胞增殖的影响

Effects of metformin on proliferation of human endometrial carcinoma cells in vitro

关键词:  子宫内膜肿瘤  二甲双胍  ERa  PTEN

Key words:  endometrial carcinoma  metformin  ERα  PTEN

摘要:

目的 流行病学研究表明二甲双胍可以降低糖尿病患者患癌的风险性和癌症相关的死亡率，本实验进一步探讨二甲双胍在体外对人子宫内膜癌细胞增殖的影响及其可能的作用机制。方法 二甲双胍干预人子宫内膜癌Ishikawa和HEC-1A细胞不同时间后，采用MTT法检测其对细胞增殖的影响，流式细胞术检测细胞周期和凋亡,Western Wotting法检测ERα及PTEN的表达。结果 二甲双胍显著抑制两种子宫内膜癌Ishikawa和HEC-1A细胞的增殖。流式细胞术检测显示二甲双胍使子宫内膜癌细胞停滞在G₀/G₁,期，并且可以诱导细胞的凋亡。Western blotting法检测显示二甲双胍能够促进子宫内膜癌细胞ERα的表达;Ishikawa细胞无PTEN蛋白的表达， HEC-1A细胞则高表达PTEN。结论 二甲双胍能抑制子宫内膜癌细胞的生长，其作用机制可能与促进ERα的表达有关。

Abstract:

Objective To investigate the effect of metformin on proliferation of human endometrial carcinoma cell lines and the underlying mechanisms. Methods Human endometrial carcinoma cell lines Ishikawa and HEC-1 A were used in the study. Cell proliferation was measured by MTT assay after exposure to metformin. Cell cycle progression and apoptosis were detected by flow cytometry. The expression of ERα and PTEN in Ishikawa and HEC-1 A cells were evaluated by Western blotting. Results Metformin significantly inhibited proliferation of Ishikawa and HEC-1 A cells. Treatment with metformin resulted in G₀/G₁ arrest, induction of apoptosis of both cell lines. Western blotting demonstrated that metformin increased the expression of ERα in two endometrial carcinoma cell lines. PTEN was highly expressed in HEC-1A cells but not expressed in Ishikawa cells. Conclixaon Metformin inhibits cell proliferation in human endometrial carcinoma cell lines, which is associated with up-regulation of ERα expression.