Notch信号通路对肝癌细胞迁移能力及E-cadherin,COX-2表达的影响

Effects of Notch Signaling Pathway on Migration Ability and Expression of E-cadherin and COX-2 in Human Hepatocel Lular Carcinoma Cells

目的:探讨Notch信号通路对肝癌细胞迁移能力及钙粘附蛋白E(E-cadherin)、环氧化酶-2(COX-2)表达的影响。方法:体外培养肝癌细胞系(SMMC-7721、MHCC97H)、正常非肿瘤肝细胞系(HL-7702),Transwell小室用于测定细胞的迁移侵袭能力,Western blot蛋白印迹法用于测定Notch1、E-cadherin、COX-2蛋白的表达水平,并采用DAPT阻断Notch信号通路,比较肝癌细胞系与正常非肿瘤肝细胞系的迁移侵袭能力及肝癌细胞中E-cadherin、COX-2蛋白的表达水平的改变。结果:SMMC-7721细胞、MHCC97H细胞的迁移能力强于HL-7702细胞,差异有统计学意义(P<0.05);相比于HL-7702细胞,MHCC97H细胞、SMMC-7721细胞中的Notch1、COX-2表达水平均显著升高,E-cadherin的表达水平明显降低(P<0.05);DAPT处理后,SMMC-7721细胞、MHCC97H细胞发生迁移的能力均弱于对照组,差异有统计意义(P<0.05);DAPT处理后,SMMC-7721细胞、MHCC97H细胞内COX-2、Notch1的表达量明显降低,而E-cadherin的表达水平升高(P<0.05)。结论:Notch信号通路参与肝癌细胞迁移过程,其机制可能与E-cadherin、COX-2的表达相关。

Objective：To investigate the impact of Notch signaling pathway on the migration of human hepatic carcinoma cells and the expression of E-cadherin and COX-2 in these cells.Methods：Cultured hepatic carcinoma cell lines（SMMC-7721,MHCC97H）,and normal non tumor liver cell line（HL-7702） in vitro.Transwell cell was used to measure the cell＇s capacity of invasion and migration.Western blot was used to measure the expression level of Notch1,E-cadherin,COX-2 protein.DAPT was used to block the Notch signaling pathway,and compared the ability of invasion and migration between hepatic carcinoma cell lines and normal non tumor liver cell line,and the change of expression level of E-cadherin and COX-2 protein in hepatic carcinoma cells.Results：The migration ability of SMMC-7721 cells and MHCC97 H cells were higher than HL-7702 cells,the difference was statistically significant（P0.05）;Compared to HL-7702 cells,the expression level of Notch1 and COX-2 in MHCC97 H cells and SMMC-7721 cells significantly increased,the expression level of E-cadherin decreased significantly（P0.05）;After DAPT treatment,the migration ability of SMMC-7721 cells,MHCC97 H cells were weaker than the control group,the difference was statistically significant（P0.05）;After DAPT treatment,the expression of COX-2 and Notch1 in SMMC-7721 and MHCC97 H cells decreased significantly,while the expression of E-cadherin significantly increased（P0.05）.Conclusion：Notch signaling pathway plays an important role in the process of liver cancer cell migration and invasion,and its mechanism is related to the expression of E-cadherin and COX-2.