Hedgehog信号传导通路在肝癌发生中的作用

Role of Hedgehog signaling pathway activation in hepatocellular carcinoma for mation

目的研究Hedgehog信号传导通路在肝癌发生中的作用,以及抑制该通路对肿瘤细胞生长的影响。方法用免疫组织化学的方法研究了14例肝癌组织切片;使用RT-PCR和Western blot方法分别研究了9例新鲜肝癌组织标本、4个肝癌细胞系和正常肝二倍体细胞中Hedgehog信号传导通路成员的转录和表达情况。结果免疫组织化学染色显示14例肝癌组织切片中,Hedgehog信号传导通路成员Gli阳性6例(42·9%),Ptch阳性10例(71·4%),Ihh阳性10例(71·4%),Smo阳性12例(85·7%)。RT-PCR和Western blot的结果显示,在肝癌组织和肝癌细胞系中,Ihh、Ptch、Smo、Gli、Hip基因的转录和蛋白表达可检测到差异。环耙明(KAAD-cyclopamine)可使Hedgehog信号传导通路各成员的表达出现不同程度的降低。结论原发性肝癌中Hedgehog信号传导通路是活化的,环耙明有阻断Hedgehog信号传导通路的作用。

Objective To investigate the role of Hedgehog signaling pathway activation in hepatocellular carcinoma formation. Methods Studied 14 HCC tissue slices,9 fresh HCC tissue samples,4 HCC cell lines and a normal hepatic cell line by using immunochemistry, Western blot and RT-PCR. Results Immunochemistry showed that in 14 HCC tissue slices,the positive ratio of the components of the Hedgehog signaling pathway Gli, Ptch, Ihh and Smo is 42. 9% ,71.4% ,71.4% and 85.7% , respectively. Western blot, RT-PCR detected difference in the expression of the Hedgehog signaling pathway components. KAAD-eyclopamine, a specific inhibitor of the Hedgehog signaling pathway, can result in the down regulation of the expression of main Hedgehog signaling pathway components. Conclusions In HCC, the Hedgehog signaling pathway is often abnormally activated, KAAD-cyclopamine can specifically inhibit the Hedgehog signaling pathway.