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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 study the role of Hedgehog signal transduction pathway in the development of hepatocellular carcinoma and its effect on the growth of tumor cells. Methods Immunohistochemical methods were used to study the histological sections of 14 cases of HCC; RT-PCR and Western blot were used to study the Hedgehog signaling pathways in 9 cases of fresh HCC tissues, 4 HCC cell lines and normal liver diploid cells, respectively. Transcription and expression of members. Results Immunohistochemical staining showed that Hedgehog signaling pathway members were positive in 6 cases (42.9%), Ptch positive in 10 cases (71.4%), and Ihh positive in 10 cases (71.4%). Smo positive in 12 cases (85.7%). The results of RT-PCR and Western blot showed that differences in the transcription and protein expression of Ihh, Ptch, Smo, Gli, and Hip genes could be detected in HCC and HCC cell lines. KAAD-cyclopamine reduces the expression of Hedgehog signaling pathway members to varying degrees. Conclusion The Hedgehog signaling pathway is activated in primary liver cancer. Cyclopamine can block the Hedgehog signaling pathway.