氯离子通道蛋白1调控放射抵抗食管鳞癌细胞放射敏感性的机制  

The mechanism of chloride intracellular ion channel 1( CLIC1) regulate the radiosensitivity of radioresistant cells of esophageal squamous cell carcinoma

作　　者：张静平[1] 陈鑫[2] 惠蓓娜[2] 孟君琦 张晓智[2] 

机构地区：[1]西安交通大学第一附属医院影像科,陕西西安710061 [2]西安交通大学第一附属医院放疗科,陕西西安710061

出　　处：《现代肿瘤医学》2016年第20期3192-3196,共5页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:30972962)

摘　　要：目的:探讨氯离子通道蛋白1(chloride intracellular ion channel 1,CLIC1)对食管鳞癌细胞获得性放射抵抗特性的影响及作用机制。方法:采用蛋白印记法及逆转录聚合酶链式反应法检测Eca109R50Gy细胞中CLIC1的表达水平。采用CLIC1小分子特异抑制剂IAA-94(indanyloxyacetic acid-94,IAA-94)抑制Eca109R50Gy细胞中CLIC1功能,通过克隆形成试验、流式细胞仪分析对比CLIC1功能抑制前后的细胞存活分数(SF)、细胞凋亡比率及细胞周期分布。结果:Eca109R50Gy细胞中CLIC1在转录水平及蛋白水平均呈现显著高表达(P<0.001);CLIC1功能抑制组Eca109R50Gy细胞克隆形成能力明显受抑(SF_(IAA-94vs) SF_(Control),P<0.001),而细胞凋亡比率显著增高(P<0.01)。CLIC1功能抑制组Eca109R50Gy细胞G2/M期细胞比例显著增加(P<0.01)。结论:CLIC1在放射抵抗的食管鳞癌细胞中高表达并与其获得性放射抵抗特性有关,抑制CLIC1功能可增强放射抵抗的食管癌细胞对放射线的敏感性,其增敏机制与影响细胞周期分布有关。Objective： To investigate the impact of CLIC1 upon the acquired radioresistance of radioresistant e-sophageal cancer Ecal09R50Gy cells and its mechanism. Methods ： Western - blot and RT - PCR were employed to observe the expression pattern of CLIC1 protein and mRNA in Ecal09R50Gy cells. Colony formation assay and Flow cytometry was used to analyse the cell survival fraction, cell apoptosis ratio and cell cycle distribution before or after CLIC1 function was inhibited with specific small molecular inhibitor indanyloxyacetic acid -94（IAA -94）. Results：CLIC1 was statistically significantly overexpressed in Ecal09R50Gy cells in both transcriptional level and protein lev- el（P 〈0. 001） . Ecal09R50Gy cells displayed significantly suppressed colony formation capability when CLIC1 func-tion was inhibited with IAA -94 compared with the control group（SF1AA_94 vs SFGon ,P 〈0. 001） ,in addition, signifi-cantly highly increased cell apoptosis ratio（ P 〈 0. 01 ） and G2/M phase distribution compared with the control group （P 〈0. 01）. Conclusion： CLIC1 was significantly overexpressed in radioresistant cells of esophageal squamous cell carcinoma and contribute to its acquired radioresistance. Inhibiting the function of CLIC1 could increase the radiosen-sitivity of the radioresistant esophageal cancer cells, and its mechanism may be correlated with regulating the cell cycle distribution.

关 键 词：氯离子通道蛋白1 食管鳞癌 放射敏感性 细胞周期 

分 类 号：R735.1[医药卫生—肿瘤]