辣椒素提高胆管癌细胞对5氟尿嘧啶的敏感性

摘要

Objective To study the role of capsaicin on improving the sensitivity of cholangiocarcinoma (CCA) cells to 5 fluorouracil(5-FU)and to investigate its molecular mechanism.Methods The MTT and animal experiment were performed to study the effect of capsaicin on the sensitivity of CCA cells to 5-FU,and the q-PCR and Western blot were performed to study its molecular mechanism.Results The effect of 5-FU inhibiting the growth of CCA cells and in vivo was significantly enhanced by capsaicin (60 μmol/L),as well as the apoptosis induced by 5-FU (P ＜ 0.01).In molecular mechanism study,capsaicin down-regulated the expression of beclinl and atg5,but inhibited the 5-FU-induced autophagy of CCA cells.In addition,capsaicin effectively increased the phosphorylation levels of S6 (S235/236) and AKT (S473).Conclusions Capsaicin can promote cell apopto sis and inhibit cell autophagy to improve the sensitivity of CCA cells to 5-FU significantly,which maybe associated with the activation of PI3K/AKT/mTOR pathway in CCA cells.%目的 研究辣椒素提高胆管癌细胞对5氟尿嘧啶(5-FU)的敏感性及其分子机制.方法 运用MTT法和动物实验检测辣椒素对胆管癌细胞5-FU药敏性的影响;采用实时荧光定量PCR (q-PCR)和Western blot技术研究辣椒素提高胆管癌细胞5-FU药敏性的分子机制.结果 辣椒素(60μmol/L)显著增强5-FU抑制胆管癌细胞体外增殖和体内成瘤效果(P＜0.05),提高5-FU在体内外诱导胆管癌细胞凋亡的能力(P＜0.05);通过对其分子机制研究发现,辣椒素可下调自噬相关基因beclin1和atg5,显著抑制5-FU诱导的胆管癌细胞自噬(P＜0.05).进一步研究发现,辣椒素可诱导AKT(S473)和S6(235/236)的磷酸化水平升高.结论 辣椒素可通过促进细胞凋亡和抑制细胞自噬显著提高胆管癌细胞对常规化疗药物5-FU的敏感性,这可能与其激活PI3K/AKT/mTOR信号通路有关.