本文關(guān)鍵詞： 膽管腫瘤 辣椒素 -氟尿嘧啶 凋亡 自噬　出處：《實(shí)用醫(yī)學(xué)雜志》2017年22期 　論文類型：期刊論文

【摘要】：目的研究辣椒素提高膽管癌細(xì)胞對(duì)5氟尿嘧啶(5-FU)的敏感性及其分子機(jī)制。方法運(yùn)用MTT法和動(dòng)物實(shí)驗(yàn)檢測(cè)辣椒素對(duì)膽管癌細(xì)胞5-FU藥敏性的影響;采用實(shí)時(shí)熒光定量PCR(q-PCR)和Western blot技術(shù)研究辣椒素提高膽管癌細(xì)胞5-FU藥敏性的分子機(jī)制。結(jié)果辣椒素(60μmol/L)顯著增強(qiáng)5-FU抑制膽管癌細(xì)胞體外增殖和體內(nèi)成瘤效果(P0.05),提高5-FU在體內(nèi)外誘導(dǎo)膽管癌細(xì)胞凋亡的能力(P0.05);通過對(duì)其分子機(jī)制研究發(fā)現(xiàn),辣椒素可下調(diào)自噬相關(guān)基因beclin1和atg5,顯著抑制5-FU誘導(dǎo)的膽管癌細(xì)胞自噬(P0.05)。進(jìn)一步研究發(fā)現(xiàn),辣椒素可誘導(dǎo)AKT(S473)和S6(235/236)的磷酸化水平升高。結(jié)論辣椒素可通過促進(jìn)細(xì)胞凋亡和抑制細(xì)胞自噬顯著提高膽管癌細(xì)胞對(duì)常規(guī)化療藥物5-FU的敏感性,這可能與其激活PI3K/AKT/mTOR信號(hào)通路有關(guān)。
[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.
【作者單位】： 廈門中醫(yī)院病理科;廈門中醫(yī)院肝病中心/肝外科;
【基金】：福建省科技計(jì)劃項(xiàng)目青年創(chuàng)新基金項(xiàng)目(編號(hào):2016D23) 福建中醫(yī)藥大學(xué)校管課題資助項(xiàng)目(編號(hào):xb2015039)
【分類號(hào)】：R735.8
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本文編號(hào)：1495176