白藜芦醇下调ILK/β-catenin信号通路抑制卵巢癌细胞增殖的机制研究

Inhibitory effect of resveratrol on proliferation of ovarian cancer cells by down-regulating ILK/β-catenin signaling pathway

摘要:

目的：探讨白藜芦醇对卵巢癌A2780细胞生长、增殖的影响，并探讨其可能机制。方法：体外培养人卵巢腺癌A2780细胞，用不同浓度（50、100、200、400 μmol/L）白藜芦醇作用A2780细胞不同时间（24、48和72 h）。采用MTT法检测白藜芦醇对细胞增殖活力的影响，采用流式细胞术检测白藜芦醇对细胞周期的改变情况，采用Western blot检测细胞内整合素蛋白激酶（integrin-linked kinase，ILK）、β-连环蛋白（β-catenin）和细胞周期蛋白D1（Cyclin D1）蛋白水平的表达。结果：200 μmol/L的白藜芦醇作用24 h可有效抑制A2780细胞增殖，使其阻滞于G0/G1期，并且存在显著的剂量-时间依赖性（P<0.05）；结果还显示白藜芦醇能够显著抑制卵巢癌A2780细胞内ILK、β-catenin和Cyclin D1蛋白表达水平（P<0.05），且存在浓度-时间依赖性（P<0.05）。结论：白藜芦醇可通过抑制卵巢癌A2780细胞中ILK/β-catenin信号通路，并降低下游靶蛋白Cyclin D1的表达，从而抑制卵巢癌细胞增殖。

Abstract:

Objective：To investigate the effect of resveratrol on the proliferation of ovarian cancer A2780 cells，and to explore its possible mechanism. Methods：Human ovarian adenocarcinoma A2780 cells were cultured in vitro and treated with different concen－trations of resveratrol（50，100，200，400 μmol/L） for 24，48 and 72 h. MTT assay was used to detect cell proliferation and cell cycle changes was determined by flow cytometry. Western blot was used to detect the expression of integrin-linked kinase（ILK），β-catenin and Cyclin D1 in cells. Results：At 200 μmol/L for 24 h，resveratrol effectively inhibited the proliferation of A2780 cells，and the cells were blocked in G0/G1 phase，and they were in a significant dose-time dependence（P<0.05）. Western blot results showed that resver－atrol significantly lowered the expression of ILK，β-catenin and Cyclin D1 at protein levels in A2780 cells（P<0.05），with a concentra－tion-time dependence（P<0.05）. Conclusion：Resvertrol could inhibit the proliferation of ovarian cancer cells by inhibiting ILK/β-catenin signaling pathway and reducing the expression of downstream target protein Cyclin D1 in A2780 cells.