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PI3K-Akt信号通路阻抑对结肠癌细胞LS-174T顺铂耐药逆转机制的研究
引用本文:杨玉捷,孟辉,杨国嵘,薛永杰,郁蓉,贺雪娇,罗菲,惠玲,张方信.PI3K-Akt信号通路阻抑对结肠癌细胞LS-174T顺铂耐药逆转机制的研究[J].第四军医大学学报,2009(23):2739-2741.
作者姓名:杨玉捷  孟辉  杨国嵘  薛永杰  郁蓉  贺雪娇  罗菲  惠玲  张方信
作者单位:兰州军区总医院消化科;兰州军区总医院胸外科;解放军第一医院病理科;兰州军区总医院医学实验中心;
基金项目:全军“十一五”课题(06MA089)
摘    要:目的:观察抑制磷脂酰肌醇3激酶和(或)蛋白激酶B(PI3K-Akt)信号通路对顺铂耐药结肠癌细胞株LS-174T细胞核中Y-Box结合蛋白1(Y-Box binding protein-1,YB-1)的活性的影响及肿瘤细胞顺铂耐药性的改变.方法:采用顺铂(cisplatin,DDP)药物浓度递增法、间歇性作用的体外诱导法建立人结肠癌的顺铂耐药细胞系LS-174T/DDP,药物Ly294002阻断PI3K-Akt信号通路传导后,采用Western Blot方法检测耐药肿瘤细胞磷酸化Akt表达水平,电泳迁移改变分析(EMSA)方法检测其核中转录因子YB-1活性的改变,MTT法检测DDP对细胞增殖的抑制率,流式细胞仪检测细胞凋亡.结果:阻断PI3K-Akt信号通路后,顺铂耐药细胞株中磷酸化Akt蛋白表达水平显著下降,同时其细胞核中YB-1的活性明显降低,且细胞的生长抑制率及细胞凋亡率均明显升高(P〈0.01).结论:阻断PI3K-Akt信号通路能够提高顺铂耐药细胞株对顺铂的敏感性,PI3K-Akt信号通路可能通过激活YB-1在肿瘤顺铂耐药机制中发挥重要作用.

关 键 词:PI3K-Akt信号通路  Y-Box结合蛋白1  人结肠癌  获得性顺铂耐药

Effects of blocking PI_3K-Akt signal pathway in reversion of cisplatin resistance in colon adenocarcinoma cell line
YANG Yu-Jie,MENG Hui,YANG Guo-Rong,XUE Yong-Jie,YU Rong,HE Xue-Jiao,LUO Fei,HUI Ling,ZHANG Fang-Xing.Effects of blocking PI_3K-Akt signal pathway in reversion of cisplatin resistance in colon adenocarcinoma cell line[J].Journal of the Fourth Military Medical University,2009(23):2739-2741.
Authors:YANG Yu-Jie  MENG Hui  YANG Guo-Rong  XUE Yong-Jie  YU Rong  HE Xue-Jiao  LUO Fei  HUI Ling  ZHANG Fang-Xing
Institution:YANG Yu-Jie1,MENG Hui2,YANG Guo-Rong3,XUE Yong-Jie3,YU Rong3,HE Xue-Jiao3,LUO Fei3,HUI Ling4,ZHANG Fang-Xing1 1Department of Gastroenterology,2Department of Cardiothoracic Surgery,4Center for Medical Experiment,Lanzhou General Hospital,Lanzhou Military Area Command,Lanzhou 730050,China,3Department of Pathology,No.1 hospital of PLA,Lanzhou 730030
Abstract:AIM:To evaluate whether Ly294002,suppressing phosphatidylinositol 3 kinase PI3K/Akt survival signaling pathway,can affect the level of YB-1 activity in the nuclei of acquired cisplatin-resistant colon adenocarcinoma cell line and subsequently restore the sensitivity of acquired cisplatin-resistant colon adenocarcinoma cell line to cisplatin(DDP).METHODS:A LS-174T cell line resistant to cisplatin was successfully established by exposing cells to increasing cisplatin concentrations ranging from 0.1 to 0.8 mg/...
Keywords:PI3K/Akt pathway  nuclear YB-1  human colon carcinoma  acquired cisplatin resistance  
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