辣椒素提高胆管癌细胞对5氟尿嘧啶的敏感性
发布时间:2018-02-08 09:55
本文关键词: 胆管肿瘤 辣椒素 -氟尿嘧啶 凋亡 自噬 出处:《实用医学杂志》2017年22期 论文类型:期刊论文
【摘要】: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(P0.05),提高5-FU在体内外诱导胆管癌细胞凋亡的能力(P0.05);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(P0.05)。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。
[Abstract]:Objective to study the effect of capsaicin on the sensitivity of cholangiocarcinoma cells to 5-FU and its molecular mechanism. Methods the effects of capsaicin on 5-FU drug sensitivity of cholangiocarcinoma cells were detected by MTT assay and animal experiments. The molecular mechanism of capsaicin in enhancing the drug sensitivity of cholangiocarcinoma cell line 5-FU was studied by real-time fluorescence quantitative PCR and Western blot. Results capsaicin 60 渭 mol / L significantly enhanced 5-FU 's inhibition of proliferation in vitro and tumor formation in vivo (P0.05N), and increased 5-FU activity. The ability of inducing apoptosis of cholangiocarcinoma cells in vivo and in vitro was found by the study of its molecular mechanism. Capsaicin down-regulated autophagy associated genes beclin1 and atg5, and significantly inhibited 5-FU-induced autophagy P0.05 in cholangiocarcinoma cells. Conclusion capsaicin can significantly increase the sensitivity of cholangiocarcinoma to 5-FU by promoting apoptosis and inhibiting autophagy, which may be related to its activation of PI3K/AKT/mTOR signaling pathway.
【作者单位】: 厦门中医院病理科;厦门中医院肝病中心/肝外科;
【基金】:福建省科技计划项目青年创新基金项目(编号:2016D23) 福建中医药大学校管课题资助项目(编号:xb2015039)
【分类号】:R735.8
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本文编号:1495176
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