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

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 M HCC‐97H 为研究对象，运用 M TT 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。

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

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 Hepa‐toma cell line HepG2 ,SMMC‐7721 ,M HCC‐97H were used for the research .The effect of Sal combined with 5‐FU on the cell pro‐liferation inhibition rate ,colony formation ,apoptosis and tumor stem cell proliferation were detected by the M TT assay ,colony for‐mation 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 ap‐optosis ,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 hepato‐cellular 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 .