抑制STAT3增强对吉非替尼耐药的非小细胞肺癌药物敏感性的研究  

Improving the drug susceptibility of gefitinib-resistant in non-small cell lung cancer by inhibiting the STAT3 activity

作　　者：王竞[1] 姜斌[1] 郭跃辉[1] 时婧[1] 公小迪[1] 

机构地区：[1]上海交通大学医学院附属第三人民医院肿瘤科,上海201900

出　　处：《蚌埠医学院学报》2013年第4期384-388,共5页Journal of Bengbu Medical College

基　　金：上海市科学技术委员会基金资助项目(10JC1409200);上海市宝山区科技发展基金项目(10-E-3);上海交通大学医学院院基金资助项目(SYZ2011-05)

摘　　要：目的:探讨非小细胞肺癌(NSCLC)中表皮生长因子受体T790M突变导致的吉非替尼耐药与信号转导及转录激活因子3(STAT3)的相关性。方法:不同浓度STAT3特异性抑制剂JSI-124处理NSCLC H1975细胞和PC9细胞后,CCK-8法检测细胞抑制率,Western blot法检测蛋白水平表达,RT-PCR法检测相关基因mRNA水平的表达。结果:NSCLC中EGFR T790M突变的H1975细胞中STAT3的表达明显高于PC9细胞(P<0.01);JSI-124可剂量和时间依赖性地抑制H1975突变细胞中STAT3的活性,并能增强其对吉非替尼的敏感性。且此现象未在对吉非替尼敏感的PC9细胞中观察到。结论:STAT3因子与表皮生长因子受体T790M突变导致的吉非替尼耐药机制相关,抑制STAT3活性可逆转吉非替尼耐药。Objective：To explore the correlation of the drug susceptibility of gefitinib-resistant in non-small cell lung cancer（NSCLS） induced by T790M mutation in EGFR and signal transducers and activators of transcription 3 （ STAT3 ）. Methods ： H1975 and PC9 cells were dealed with different concentrations of STAT3 specific inhibitor JSI-124. The inhibition rate of cells and the levels of protein and mRNA of relative factors were determined by CCK-8 ,Western blot and RT-PCR,respectirely. Results ：The STAT3 expression of H1975 cells with EGFR T790M mutation of NSCLC were obviously higher than that in PC9 ceils（ P 〈 0.01 ）. JSI-124 inhibited the activity of STAT3 in H1975 mutation cells in dose-and time-dependent manner and improved the susceptibility of gefitinib, but not for PC9 cells. Conclusions ：The gefitinib-resistant mechanism induced by T790M mutation in EGFR is related to STAT3, which can be reversed by inhibiting the STAT3 activity.

关 键 词：癌 非小细胞肺 吉非替尼 耐药性 信号转导及转录激活因子3 

分 类 号：R734.2[医药卫生—肿瘤]