糖原合酶激酶3-β对胃癌细胞生长周期和转移的影响

Effect of GS K-3β on the cell cycle and metastasis of human gastric carcinoma cell

目的:探讨GSK-3β功能改变对胃癌细胞生长周期和转移的影响。方法:LY294002单独或联合LiCl影响胃癌细胞株SCG-7901GSK-3β活性,Western blotting检测总GSK-3β、p-GSK-3βser9表达,MTT和FCM检测细胞增殖及周期分布,细胞免疫化学检测E-cadherin、β-catenin表达,细胞粘附实验观察细胞与基质的粘附力。结果:LY294002干预细胞72h后,总GSK-3β表达无改变,p-GSK-3βser9表达下降;增殖受抑制;细胞周期阻滞于G0/G1期;E-cadherin表达增高,β-catenin表达下降;细胞与基质粘附力降低。LiCl部分拮抗LY294002对细胞的生长抑制、周期阻滞及对E-cadherin、β-catenin表达的改变和细胞与基质粘附力的影响。结论:GSK-3β可促进胃癌细胞G1-S期周期阻滞、抑制细胞生长并可上调E-cadherin表达抑制细胞转移。

Objective： To observe the effect of GSK-3β on the cell cycle and metastasis of human gastric carcinoma cell. Methods： Influencing the GSK-3β activity of human gastric carcinoma cell line SCG-7901 by LY294002 with or with not LiCl treatment. The expression of total GSK-3β and p-GSK-3β^ser9 were detected in protein level by western blotting, cell proliferation and cell cycle distribution were tested by MTF and FCM respectively, the expression of E-cadherin and β-catenin were measured with S-P immunohistochemistry and the cell-ground substance adhesion was tested by cell adherence assay. Results： The expression of total GSK-3β was constant and the protein level of p-GSK-3β^ser9 was down regulated after exposured to LY294002 by 72 h,the cell proliferation was inhibited , cell cycle was arrest at G0/G1 phase,the E-cadherin level was positively regulated,the expression of β-catenin and the adhesion rate were decreased. The effect on the proliferation,cell cycle,the expression of E-cadherin and β -catenin and the adhesion by the LY294002 were partially abrogated by lithium chloride. Conclusion： GSK-3β could negatively regulate the proliferation of human gastric carcinoma cell by leading cells to GI-S arrest and inhibit its metastasis by positively regulating the expression of E-cadherin.