Hedgehog信号通路对某些消化道肿瘤细胞生长的调节作用

Hedgehog signaling pathway regulates growth of human digestive tract tumor cells

目的: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。

Objective：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.