Hedgehog信号通路与Snail在肝癌细胞系中的表达及意义

Expression of Hedgehog Signaling Pathway in Hepatoma Cell Lines and Its Relation with Snail

目的探讨Hedgehog(Hh)信号通路在各种肝癌细胞系中的表达及其与Snail蛋白的关系。方法用RT-PCR检测了Hh信号通路分子Shh、Ihh、Ptch-1、Smo、Gli-1、Gli-2、Gli-3 mRNA在4种肝癌细胞系HepG2、Hep3B、SMMC-7721、Huh-7和永生化肝细胞系L02中的表达情况,应用Western blot检测了Snail蛋白在SMMC-7721和L02细胞中的表达差异。结果RT-PCR结果显示Hedgehog信号通路分子mRNA在肝癌细胞株中呈高表达,并以Shh信号为主;Gli-2在SMMC-7721细胞中表达最显著,而在正常肝细胞株L02中表达最弱,两者差异显著(P<0.01)。Snail蛋白在SMMC-7721细胞中的表达显著高于L02细胞(P<0.05),且与Gli-2的表达呈正相关(P<0.05)。结论Hh信号通路可能通过Gli-2上调Snail的表达,增强肝癌细胞增殖力和侵袭力,促进肝细胞癌的发生和发展。

Objective To study the expression of Hedgehog（Hh） signaling pathway in 5 hepatoma cell lines and its relation with Snail.Methods The mRNA expression of Hh signaling pathway components,Shh,Ihh,Ptch-1,Smo,Gli-1,Gli-2 and Gli-3,was detected by RT-PCR,and the protein expression of Snail by Western blot in SMMC-7721 and L02 cells respectively.Results The mRNA expression of Hh signaling pathway components was robustly observed in hepatoma cell lines,with predominance in Shh signaling;Gli-2 was significantly overexpressed in SMMC-7721 but obviously weaker expression in normal liver cell lines（L02） was detected（P0.01）.The expression of Snail in SMMC-7721 cells was higher than that in L02 cells（P0.05）,and there was significant positive correlation only between the expression of Gli-2 and Snail（P0.05）.Conclusion Hh signaling pathway up-regulates Snail by Gli-2,which enhances proliferation and invasion of HCC cells,and plays a crucial role in occurrence and development of hepatocellular carcinoma.