Effect of abnormal Hedgehog signaling pathway on multidrug resistance of human colon adenocarcinoma cells / 肿瘤

ABSTRACT

Objective: To investigate the correlation between Hedgehog (Hh) signaling pathway and multidrug resistance of human colon adenocarcinoma cells. Methods: Human colon adenocarcinoma cell line HCT-8 and its vincristine (VCR)-resistant variant HCT-8/VCR cells were treated by agonist SAG or antagonist GANT61 of Hh signaling pathway, respectively. Four groups were designed for the purpose of this study HCT-8 group, HCT-8/VCR group, HCT-8+SAG group (treated with 3 nmol/L SAG for 48 h), and HCT-8/VCR+GANT61 group (treated with 5 μmol/L GANT61 for 48 h). Then CCK-8 (cell counting kit-8) assay was used to detect the multidrug resistance and the survival rate of the cells. The expression levels of Hh signaling members Smo (Smoothened protein) and Gli1 (Gloma-associated oncoprotein-1) and P-gp (P-glycoprotein) mRNAs and proteins were determined by real-time fluorescence quantitative PCR and Western blotting, respectively. Results: The expressions of Smo, Gli1 and P-gp mRNAs and proteins in HCT-8/VCR group were higher than those in HCT-8 group (P < 0.05). Compared with HCT-8 group, the survival rate and the mRNA and protein expression levels of Smo, Gli1 and P-gp in HCT-8+ SAG group were significantly up-regulated (P < 0.05). Compared with HCT-8/VCR group, the survival rate and the mRNA and protein expression levels of Smo, Gli1 and P-gp in HCT-8/VCR+GANT61 group were significantly down-regulated (P < 0.05). Conclusion: The multidrug resistance of human colon adenocacinoma cells may be correlated with abnormal activation of Hh signaling pathway. Copyright © 2012 by TUMOR.