Notch信号通路参与肝癌细胞侵袭迁移的机制分析

Mechanism of Notch signaling pathway in the migration and invasion of hepatocellular carcinoma cells

目的:探讨Notch信号通路在肝癌细胞侵袭迁移过程中的相关机制。方法:体外培养肝癌细胞系Hep G2、Huh-7和正常非肿瘤肝细胞系HL-7702,利用Transwell小室检测细胞的侵袭迁移能力,Western blot方法检测Notch1、Snail、E-cadherin、MMP-2、MMP-9的蛋白表达。采用1μmol/L和5μmol/L的DAPT(γ-分泌酶抑制剂)阻断Notch信号通路,与对照组(空培养基)比较对细胞的侵袭迁移能力以及Snail、E-cadherin、MMP-2、MMP-9表达量的影响。结果:Notch1、Snail、E-cadherin、MMP-2、MMP-9参与了肝癌细胞侵袭迁移过程,DAPT能显著上调E-cadherin和下调Snail、MMP2、MMP-9的表达(P<0.05)。结论:Notch信号通路在肝癌细胞侵袭迁移过程中起着非常重要的作用,其机制初步认为与Snail、E-cadherin、MMP-2、MMP-9的表达有关。

Objective： To explore the relate mechanism of Notch signaling pathway in the migration and invasion of hepatocellular carcinoma cells. Methods： Cultured human hepatoma Hep G2,Huh- 7 and Normal liver HL- 7702 cells in vitro, Using Transwell assay to test the ability of cell invasion and migration; Using Western Blot to detect the protein expression of Notch1, Snail, E- cadherin,MMP- 2 and MMP- 9. Moreover, compared the cell invasion and migration ability before and after blocking Notch signaling pathway with 1 μmol/L and 5 μmol/L DAPT（γ secretase inhibitors）. Results： Both Notch1, Snail, E- cadherin, MMP- 2 and MMP- 9 were involved in the invasion and migration process of HCC cells, The effect of DAPT could up- regulate the expression of E- cadherinand down-regulate the expression of Snail,MMP2 and MMP-9（P〈0.05）. Conclusions： The role of Notch signaling pathway in HCC cells invasion and migration is very important, and the mechanism maybe relate to the levels of Snail, E-cadherin, MMP-2 and MMP-9.