研究Hedgehog信号通路成员Shh、patched(PTCH)、smoothened(Smo)和Gli-1在结肠癌和胰腺癌细胞株以及人结肠腺瘤组织细胞中的表达情况,并探讨Smo受体特异性小分子抑制剂环靶明(cyclopamine)对这些肿瘤细胞生长的影响。方法:体外培养结肠癌细胞LS174T、HCT116、SW116、CT26和胰腺癌细胞BxPC3,并肠镜下摘取2例结肠腺瘤组织标本,提取细胞株和腺瘤组织总RNA,用RT-PCR扩增Shh,PTCH,Smo,Gli-1基因;使用MTT法检测环靶明在体外对这些肿瘤细胞生长的抑制作用。结果:在SW116、CT-26、BxPC3细胞和2例结肠腺瘤组织中Shh、PTCH、Smo和Gli-1均有不同程度的表达,而在HCT116和LS174T细胞中未能扩增出PTCH和(或)Smo基因的mRNA;环靶明对这些肿瘤细胞的生长有一定的抑制作用,且对Smo基因阳性表达细胞株的抑制作用更显著。结论:Hedgehog信号通路成员Shh、PTCH、Smo和Gli-1在结肠癌、胰腺癌及结肠腺瘤细胞中有不同程度的表达,环靶明对Smo高表达细胞的生长有明显抑制作用;提示该信号通路可能在部分消化道肿瘤细胞中被活化。

To study the expression of Shh, patched(PTCH), smoothened (Smo) and Gli 1 genes，four components of the Hedgehog signaling pathway, in colonic cancer cell lines, pancreatic cancer cell line and colonic adenoma tissues, and to discuss the influence of cyclopamine, a Smo receptor specific inhibitor, on the growth of these tumor cells. Methods: The expression of Shh, PTCH, Smo and Gli 1 were investigated using RT PCR in 4 colonic cancer cell lines (LS174T, HCT116, SW116 and CT26), pancreatic cancer cell line BxPC3 and 2 colonic adenoma tissues. MTT method was used to study the inhibitory effect of cyclopamine on the growth of these cancer cell lines in vitro . Results: Shh, PTCH, Smo and Gli 1 genes were expressed in 2 of colonic adenoma tissues and SW116, CT26 and BxPC3 cells. The mRNA of Smo and PTCH genes were not found in LS174T and HCT116 cells; the expression of Shh and Gli 1 mRNA were significantly up regulated. Cyclopamine inhibited the growth of SW116, CT 26 and BxPC3, expecially the positive cells of Smo gene. Conclusion: Shh, PTCH, Smo and Gli 1 genes are expressed in colonic cancer cell lines, pancreatic cancer cell line and colonic adenoma tissues, Cyclopamine has obvious inhibitory effect on cells with overexpression of Smo , which implies that Hedgehog signaling pathway might be activated in some tumor cells of digestive system.