Hedgehog信号通路对塞来昔布介导抗结肠癌效应的影响

Role of Hedgehog signaling pathway in celecoxib-mediated anti-colon cancer effect

目的研究Hedgehog(Hh)信号通路对环氧合酶2抑制剂塞来昔布介导抗结肠癌效应的影响。方法以胰腺癌PANC-1细胞为对照,采用MTT检测环巴胺20μmol/L和塞来昔布80μmol/L处理后的结肠癌HT-29、LoVo和HCT-116细胞存活率,ELISA法检测胞内胶质瘤相关癌基因同源物1(GLI1)的含量变化。结果环巴胺、塞来昔布均能抑制PANC-1细胞生长和GLI1的含量(P<0.05或P<0.01)。环巴胺处理结肠癌细胞后发现,HT-29和LoVo细胞存活率、GLI1含量降低(P<0.05或P<0.01);其中,LoVo细胞的抑制作用更为显著,而HCT-116细胞生长、GLI1含量无明显变化(P>0.05)。塞来昔布处理结肠癌细胞后发现,HT-29和HCT-116细胞存活率、GLI1含量降低(P<0.05或P<0.01);其中,HCT-116细胞的抑制作用更为显著,而LoVo细胞生长、GLI1含量无明显变化(P>0.05)。结论 Hh信号在LoVo和HT-29细胞是有活性的,而且该信号对LoVo细胞恶性行为维持是必须的。塞来昔布抗结肠癌细胞的作用是有选择性的,可能是通过SMO非依赖的途径来发挥抗癌作用。

Objective To investigate the role of Hedgehog （Hh） signaling pathway in cyclooxygenase-2 inhibitor celecoxib-mediated anti-colon cancer effect. Methods Taking pancreatic cancer PANC-1 cells as the controls, the viability of colon cancer HT-29, LoVo and HCT-116 cells treated with cyclopamine and celecoxib were detected by MTT assay, and glioma-associated oncogene homolog（GLI1） expression was determined by ELISA. Results Cyclopamine and celecoxib could significantly inhibit the growth of PANC-1 cells and GLI1 expression（P〈0. 05 or P〈0. 01）. When colon cancer cells were treated with cyclopamine, the cell viability and GLI1 expression in HT-29 and LoVo cells were decreased（P〈0. 05 or P〈0. 01）, which were not obviously changed in HCT-116 cells（P〉0. 05）. When colon cancer cells were treated with celecoxib, the cell viability and GLI1 expression in HT-29 and HCT-116 cells were decreased（P〈0. 05 or P〈0. 01）, which were not remarkably changed in LoVo cells（P〉0. 05）. Conclusion Hh signaling is activated in HT-29 and LoVo cells and essential for maintaining the malignant behavior of LoVo cells. Celecoxib-mediated anti-colon cancer effect is selective probably via SMO-independent modulation of GLI1 activity .