沙利霉素增强肝癌细胞对5-氟尿嘧啶敏感性及其作用机制研究

Sensitivity and mechanism of salinomycin affecting the liver cancer cells to 5-fluorouracil

目的研究沙利霉素(Sal)增强肝癌细胞对5-氟尿嘧啶(5-FU)敏感性及其机制,为抗药性原发性肝癌患者提供新的治疗方案。方法选用肝癌细胞株HepG2、SMMC-7721和MHCC-97H为研究对象,运用MTT方法,克隆形成实验,流式细胞仪检测Sal和5-FU联合作用下对肝癌细胞增殖抑制率、克隆形成、细胞凋亡和肿瘤干细胞增殖的影响;Western-blot方法检测Sal和5-FU联合作用对Wnt/β-catenin信号通路的影响。结果 Sal和5-FU联合作用能够显著抑制肝癌细胞增殖和克隆形成并诱导细胞凋亡,具有协同作用;5-FU能促进肝癌肿瘤干细胞增殖,而Sal降低5-FU的这一作用;同时Sal能抑制Wnt/β-catenin信号通路。结论 Sal通过抑制Wnt/β-catenin信号通路增强肝癌细胞对5-FU的敏感性;Sal和5-FU联合作用为抗药性原发性肝癌患者提供新的治疗方案。

Objective To study salinomycin（Sal）enhance the sensitivity of liver cancer cell to 5-fluorouracil（5-FU）and its mechanism,and to provide drug-resistant primary hepatocellular carcinoma（HCC）patients with a new treatment.Methods Hepatoma cell line HepG2,SMMC-7721,MHCC-97 H were used for the research.The effect of Sal combined with 5-FU on the cell proliferation inhibition rate,colony formation,apoptosis and tumor stem cell proliferation were detected by the MTT assay,colony formation assay,flow cytometry.And the effect on Wnt/-catenin when Sal combined with 5-FU were detected by Western-blot.Results Sal combined with 5-FU significantly inhibited the liver cancer cell proliferation and colony formation and induced cell apoptosis,showed the synergistic effect.5-FU promoted the proliferation of hepatocarcinoma stem,but Sal reduced the function of 5-FU.At the same time Sal could inhibit the Wnt/-catenin signal pathway.Conclusion The Sal can increase the sensitivity of hepatocellular carcinoma cells to 5-FU by inhibiting Wnt/-catenin signal pathway;Sal combined with 5-FU could provide drug-resistant HCC patients with a new treatment.