Sonic Hedgehog信号通路在肝癌细胞增殖中的作用

Role of Sonic Hedgehog signaling pathway in proliferation of hepatocellular carcinoma cells

目的:探讨Sonic Hedgehog(SHH)信号通路在肝癌细胞增殖中的作用及抑制该通路的活性对肝癌细胞对化疗药物敏感性的影响。方法:分别用不同浓度重组SHH N-末端肽(rSHH-N)、SHH中和抗体(anti-SHH)、SHH通路抑制剂cyclopamine作用人肝癌SMMC-7721细胞不同时间,用MTT法检测细胞增殖状态。比较5-氟尿嘧啶(5-FU)、anti-SHH、cyclopamine、anti-SHH+5-FU、cyclopamine+5-FU对SMMC-7721细胞增殖抑制作用的差异。结果:rSHH-N作用后,SMMC-7721细胞增殖明显增加,而anti-SHH和cyclopamine作用后,SMMC-7721细胞增殖明显降低,且均呈时间和浓度依赖性(均P<0.05);anti-SHH或cyclopamine联合5-FU对SMMC-7721细胞增殖抑制作用明显强于各药单用(均P<0.05)。结论:SHH信号通路在肝癌生长中起重要作用,阻断SHH信号通路能抑制肝癌细胞增殖且能增加肝癌细胞对化疗药物的敏感性。

Objective：To investigate the role of Sonic Hedgehog （SHH） signaling pathway in proliferation of hepatoceUular carcinoma （HCC） cells and the impacts of its inhibition on proliferation and chemosensitivity of HCC cells. Methods： Human HCC SMMC-7721 cells were respectively exposed to recombinant SHH N-terminus （rSHH-N）, SHH neutralizing antibody （anti-SHH）, and SHH pathway inhibitor cyclopamine for different time periods, and then the proliferation status of the cells was determined by MTT assay. The inhibitory effects on the proliferation of SMMC-7721 cells among 5-fluorouracil （5-FU）, anti-SHH, cyclopamine, anti-SHH plus 5-FU and cyclopamine plus 5-FU were compared.Results： The proliferation of SMMC-7721 cells was significantly increased after rSHH-N treatment, while it was significantly decreased after anti-SHH or cyclopamine treatment, and all the effects presented a concentration- and time-dependent manner （all P〈0.05）. The inhibitory effect of anti-SHH plus 5-FU or cyclopamine plus 5-FU was significantly greater than any of the drugs used alone （all P〈0.05）. Conclusion： SHH signaling pathway plays an important role in growth of HCC cells, and blockage of SHH signaling pathway can inhibit proliferation of HCC cells and enhance their sensitivity to chemotherapeutic drugs.