LY294002增强5-氟尿嘧啶对大肠癌细胞侵袭和转移的抑制作用

目的:探讨PI3K/Akt信号通路抑制剂LY294002及5-氟尿嘧啶(5-Fu)对大肠癌细胞转移和侵袭的影响.方法:LY294002及5-Fu体外作用于大肠癌细胞株SW480,Western blot检测总Akt和Akt-ser473蛋白表达,细胞黏附实验观察细胞与基质的黏附力,细胞划痕实验检测细胞迁移能力,Transwell法观察细胞侵袭能力,免疫细胞化学法测定β-catenin及MMP-7蛋白表达.结果:经LY294002及5-Fu处理的SW480细胞总Akt表达无改变,Akt-ser473蛋白表达下降.LY294002及5-Fu分别、并协同使细胞与基质的黏附力、细胞迁移能力及侵袭能力减弱,β-catenin及MMP-7蛋白表达水平降低.结论:LY294002可增强5-Fu对大肠癌细胞侵袭和转移的抑制作用.

LY294002 Enhances the Effect of 5-Fluorouracil Inhibition on Metastasis and Invasion of Colon Cancer Lines

Objective: To investigate the effects of LY294002,a specific inhibitor of phosphatidylnositol 3-kinase,and 5-fluorouracil on the metastasis and invasion of colon cancer lines.Methods: Human colon cancer lines SW480 were cultured with PI3K/Akt signaling pathway inhibitor LY294002 and 5-fluorouracil in vitro.The expression of total Akt and Akt-ser473 protein was detected by Western blot,the cell-ground substance adhesion ability was tested by cell adherence assay,the ability of cells' migration and invasion was measured with wound healing assays and Transwell plate,and the expression of β-catenin and MMP-7 protein were detected by SP immunohistochemistry.Results: The expression of total Akt had no changes,but the Akt-ser473 protein was down-regulated after treatment with LY294002 or 5-fluorouracil.After the treatment of LY294002 or /and 5-fluorouracil,the adhesion rate and the ability of migration and invasion were decreased,and the expression of β-catenin and MMP-7 protein were positively regulated.Conclusion: LY294002 may enhance the effect of 5-fluorouracil inhibition on metastasis and invasion of colon cancer lines.