Hedgehog信号通路在人肝细胞癌细胞系及肝癌组织中的表达与意义

目的探讨Hedgehog信号通路在人肝细胞癌细胞系及Shh基因在肝癌组织中的表达及意义。方法采用半定量RT-PCR法检测Hep3B和HCC-LM3细胞中Shh、Ihh、Ptch、Smo、Gli mRNA及21例肝细胞癌癌组织和癌旁肝组织中Shh mRNA的表达状况。结果Shh、Ihh、Ptch、Smo、Gli mRNA在两个肝癌细胞系中均有表达。其中,Shh、Gli1 mRNA在Hep3B细胞中的表达强度显著高于HCC-LM3细胞,而Gli2和Gli3的表达强度正相反;Ihh、Smo mRNA在Hep3B细胞中的表达强度高于HCC-LM3细胞,但两者间无显著性差异;Ptch mRNA在两个细胞系细胞中的表达无显著性差异;Shh mRNA在肝细胞癌癌组织中的阳性检出率为57.1%（12/21）,在癌旁组织中为4.8%（1/21）,两者间有显著性差异（P〈0.05）。其中,6例高分化、8例中分化和7例低分化肝细胞癌中Shh mRNA的阳性检出率分别为83.3%（5/6）、62.5%（5/8）和28.6%（2/7）,表现为随肝细胞癌由高到低的分化而呈显著性下降的趋势（P〈0.05）;Shh mRNA的表达强度在肝细胞癌癌组织之间、癌与癌旁组织之间无显著性差异。结论Hedgehog信号通路的异常激活参与了肝细胞癌的发生发展过程,Shh mRNA在部分高中分化肝细胞癌中表达上调,这或许为探讨肝癌的发生机制、早期诊断及治疗提供了新的依据。

Expression of Hedgehog pathway in hepatocellular carcinoma cell lines and in liver cancerous tissues GUO

Objective To detect the expression of mRNA of Hedgehog（Hh）pathway family in hepatocellular carcinoma （HCC）cell lines and the expression of Shh mRNA in surgically resected HCC tissues. Methods Semi-quantitative RT-PCR was used for detection of Shh,Ihh,Ptch,Smo and Gli mRNA in Hep3B and HCC-LM3 cell lines and Shh mRNA was detected in 21 HCC specimens. Results All the Hh pathway family was detected positive in both HCC cell lines. Significantly,the expression of Shh and Glil mRNA was higher in Hep3B than that in HCC-LM3 cell lines,while the expression of Gli2 and Gli3 was on the contrary. The expression of Ihh and Smo mRNA was higher in Hep3B than that in HCC-LM3,but not significant between them. No significance of Ptch expression was found between both cell lines;The expression rate of Shh mRNA was 57.1%（12/21） in tumor tissues,significantly higher than 4.8%（1/21） in nontumor tissues. In well- , moderately- , and poorly-differentiated HCCs,the expression of Shh mRNA was 83.3%（5/6）,62.5% （5/8）and 28.6%（2/7）,respectively,which showed less detectable in a poorly-differentiated manner. No difference of expression intensity of Shh mRNA was found among tumor tissues or between tumor and non-tumor tissues. Conclusion Activation of Hh pathway may involve in human HCC carcinogenesis. In HCCs with well and moderate differentiation,the expression of Shh mRNA was up-regulated. The study may be useful for exploring HCC carcinogenesis,early diagnosis and treatment for HCC.