二甲双胍对人肝癌细胞系HepG2增殖、迁移能力的影响及其机制探讨

Effects of metformin on proliferation and migration of human hepatoma cell line HepG2

目的 观察二甲双胍(Met)对人肝癌细胞系HepG2增殖、迁移能力的影响,并探讨其机制。方法 体外培养HepG2细胞,随机分为5组,A、B、C、D组分别加入1、5、10、50mmol/L的二甲双胍各200μL,E组给予等体积培养基,继续培养48h。MTT法测算细胞存活率,Transwell小室法检测跨膜细胞数,Western blotting法检测E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)。结果 与E组比较,A、B、C、D组细胞存活率和跨膜细胞数、Vimentin相对表达量减少,E-cadherin相对表达量增加(P均<0.05);与A组比较,B、C、D组细胞存活率和跨膜细胞数、Vimentin相对表达量减少,E-cadherin相对表达量增加(P均<0.05);与B组比较,C、D组细胞存活率和跨膜细胞数、Vimentin相对表达量减少,E-cadherin相对表达量增加(P均<0.05);与C组比较,D组细胞存活率和跨膜细胞数、Vimentin相对表达量减少,E-cadherin相对表达量增加(P均<0.05)。结论 Met能抑制HepG2细胞增殖和迁移能力,且在浓度为50mmol/L时抑制作用最大,其作用机制可能与上调E-cadherin表达及下调Vimentin表达有关。

Objective To investigate the effects of metformin (Met) on the proliferation and migration of human hepatoma cell line HepG2 and its mechanism. Methods HepG2 cells were cultured in vitro and randomly divided into 5 groups: groups A, B, C, D, and E. Cells in the groups A, B, C, and D were added with 1, 5, 10, and 50 mmol/L metformin (200 μL in each), respectively. Cells in the group E were given an equal volume of medium and were cultured for 48 h. Cell viability was measured by MTT assay, transmembrane cell number by Transwell chamber assay, and E-cadherin and Vimentin by Western blotting.Results Compared with the group E, the cell viability, transmembrane cell number and relative expression of Vimentin in the groups A, B, C and D decreased, and the relative expression of E-cadherin increased (all P <0.05);compared with the group A, the cell viability, transmembrane cell number and relative expression of Vimentin in the groups B, C and D decreased, and the relative expression of E-cadherin increased (all P <0.05);compared with the group B, the cell viability, transmembrane cell number and relative expression of Vimentin in the groups C and D decreased, and the relative expression of E-cadherin increased (all P <0.05);compared with the group C, the cell viability, transmembrane cell number and relative expression of Vimentin in the group D decreased, and the relative expression of E-cadherin increased (all P <0.05). Conclusions Met can inhibit the proliferation and migration of HepG2 cells, and the inhibitory effect is maximal at the concentration of 50 mmol/L. The mechanism may be related to up-regulation of E-cadherin expression and down-regulation of Vimentin expression.