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NVP-BEZ235诱导多囊肾大鼠胆管上皮细胞自噬的机制研究 被引量：3

NVP-BEZ235 induces autophagy of polycystic kidney rat cholangiocytes
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摘要 目的:探讨PI3K/Akt/m TOR双靶点抑制剂NVP-BEZ235诱导多囊肾(polycystic kidney,PCK)大鼠胆管上皮细胞自噬的作用。方法:免疫组化法检测p-m TOR和p-Akt在PCK大鼠胆管上皮细胞中的水平。WST-1比色法检测NVP-BEZ235对胆管细胞活力的抑制作用以及LC3、Beclin 1基因沉默和自噬特异性抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)对细胞活力的影响。蛋白免疫印迹法检测NVP-BEZ235对PI3K/Akt/m TOR信号通路相关蛋白及自噬标志蛋白LC3和Beclin 1的变化。结果:p-m TOR和p-Akt在PCK大鼠胆管上皮细胞中显著升高,NVP-BEZ235可明显抑制胆管上皮细胞的活力,且呈浓度和时间依赖性改变(P<0.05);NVP-BEZ235明显抑制PI3K/Akt/m TOR信号通路相关蛋白的水平;并上调自噬标志蛋白LC3 II/LC3 I比值和Beclin 1蛋白的表达水平。LC3、Beclin 1基因沉默和3-MA均可明显减弱NVP-BEZ235对细胞活力的抑制作用(P<0.01)。结论:NVPBEZ235可抑制PCK大鼠胆管上皮细胞的活力,其机制与自噬密切相关。 AIM： To explore the effect of dual PI3K/Akt/m TOR inhibitor NVP-BEZ235 on autophagy of polycystic kidney（ PCK） rat cholangiocytes. METHODS： The protein levels of p-m TOR and p-Akt in the bile duct epithelial cells were examined by immunohistochemistry. The effect of NVP-BEZ235 on the viability of cholangiocytes was detected by WST-1 assay. The levels of PI3 K / Akt / m TOR signaling pathway and autophagy-related proteins with NVP-BEZ235 treatment were determined by Western blot. The effects of LC3 and Beclin 1 silencing,and authophagy-specific inhibitor 3-methyladenine（ 3-MA） on the cell viability were analyzed by WST-1 assay. RESULTS： The protein levels of p-Akt and pm TOR were highly increased in the bile duct epithelium of the PCK rats. NVP-BEZ235 significantly inhibited the viability of the cholangiocytes in a dose- and time-dependent manner（ P〈0. 05）. NVP-BEZ235 significantly reduced the levels of PI3 K / Akt / m TOR signaling pathway-related proteins in the PCK rat cholangiocytes. NVP-BEZ235 upregulated the autophagy-specific proteins LC3 II and Beclin 1. The inhibitory effect of NVP-BEZ235 on the cell viability was weakened by treatment with 3-MA and knockdown of LC3 and Beclin 1（ P〈0. 01）. CONCLUSION： The PI3 K / Akt / m TOR inhibitor NVPBEZ235 suppresses the viability of PCK rat cholangiocytes,and the mechanism is closely related with autophagy.
作者 叶晶 刘特思 金贤国 朴英实 赵元媛 韩晶邑 林贞花 原田宪一 任香善
机构地区 延边大学医学院病理学教研室 延吉市中医医院消化内科 金泽大学医学部病理学教研室
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2016年第5期886-891,共6页 Chinese Journal of Pathophysiology
基金 国家自然科学基金资助项目(No.413010033) 延边大学自然科学基金资助项目(No.602013109)
关键词 自噬 PI3K/Akt/mTOR信号通路 多囊肾 NVP-BEZ235 Autophagy PI3K/Akt/m TOR signaling pathway Polycystic kidney NVP-BEZ235
分类号 R363 [医药卫生—病理学]
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参考文献17

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二级参考文献16

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共引文献23

同被引文献11

引证文献3

二级引证文献17

中国病理生理杂志
2016年 第5期

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