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Amyloid precursor protein regulates 5-fluorouracil resistance in human hepatocellular carcinoma cells by inhibiting the mitochondrial apoptotic pathway

淀粉样前体蛋白通过抑制线粒体凋亡通路调节人肝癌细胞对5-氟尿嘧啶的抗性

作     者:Xiao-long WU Ying CHEN Wen-cui KONG Zhong-quan ZHAO Xiao-long WU;Ying CHEN;Wen-cui KONG;Zhong-quan ZHAO

作者机构:Department of Oncology900 Hospital of the Joint Logistics TeamFuzhou 350025China 

出 版 物:《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报(英文版)B辑(生物医学与生物技术))

年 卷 期:2020年第21卷第3期

页      面:234-245页

核心收录:

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基  金:Project supported by the International Science&Technology Cooperation Program of China(No.2016G02) 

主  题:Amyloid precursor protein 5-Fluorouracil resistance Mitochondrial apoptotic pathway Hepatocellular carcinoma 

摘      要:Hepatocellular carcinoma(HCC)is a malignant tumor with high morbidity and mortality *** accounts for the majority of primary liver cancer *** precursor protein(APP),a cell membrane protein,plays a vital role in the pathogenesis of Alzheimer’s disease,and has been found to be implicated in tumor growth and ***,to understand the relationship between APP and 5-fluorouracil(5-FU)resistance in liver cancer,Cell Counting Kit-8,apoptosis and cell cycle assays,western blotting,and reverse transcription-quantitative polymerase chain reaction(q PCR)analysis were *** results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated,as compared with that in Bel7402 *** successful construction of APP-silenced(si APP)and overexpressed(OE)Bel7402 cell lines,data revealed that the Bel7402-APP751-OE cell line was insensitive,while the Bel7402-si APP cell line was sensitive to 5-FU in comparison to the matched control ***,APP overexpression decreased,while APP silencing increased 5-FU-induced apoptosis in Bel7402 ***,APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes(B-cell lymphoma-2(Bcl-2)and B-cell lymphoma-extra large(Bcl-xl)).Taken together,these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU,providing a new perspective for drug resistance.

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