4E-BP1在人脑胶质瘤细胞对卡氮芥获得性耐药中的作用  

4E-BP1 regulates sensitivity of human glioma cells to carmustine

作　　者：朱慧丽[1,2] 翁泽平[1,2] 张继君[1] 林琛莅[1] 谢思明[1] 王超[1] 马继伟[1] 钟雪云[1] 

机构地区：[1]暨南大学医学院病理系,广东广州510632 [2]暨南大学附属第一医院,广东广州510630

出　　处：《中国病理生理杂志》2013年第7期1192-1196,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81072059);广东省高等学校科技创新重点项目(No.CXZD1110);广东省医学科研基金资助项目(No.B2011159)

摘　　要：目的:探讨真核翻译起始因子4E结合蛋白1(4E-BP1)与人脑胶质瘤细胞耐药性的关系,为寻找克服胶质瘤获得性耐药的新靶点提供理论依据。方法:Western blotting检测SWOZ2及其获得性耐药细胞株SWOZ2-BCNU中4E-BP1及其磷酸化蛋白(p-4E-BP1)的表达。小干扰RNA下调4E-BP1表达后,细胞计数试剂盒8检测SWOZ2细胞对卡氮芥(BCNU)的耐药性。免疫荧光法检测4E-BP1及p-4E-BP1(T70)蛋白在2株细胞中的表达位置。结果:SWOZ2-BCNU细胞中4E-BP1及其磷酸化蛋白表达较SWOZ2细胞明显下降。下调4E-BP1表达能明显增加敏感细胞对BCNU的耐药性。SWOZ2-BCNU细胞p-4E-BP1(T70)蛋白在获得性耐药过程中出现了核转位。结论:4E-BP1作为翻译调控关键蛋白,可能参与了人脑胶质瘤获得性耐药的发生机制。AIM： For finding new target to overcome acquired drug resistance of glioma,the relationship between eukaryotic translation initiation factor 4E-binding protein 1（4E-BP1） and acquired drug resistance to carmustine [1,3-bis（2-chloroethyl）-1-nitrosourea,BCNU] in human glioma cells was investigated.METHODS： Western blotting was used to analyze the expression levels of 4E-BP1 and phosphorylated 4E-BP1（p-4E-BP1） in SWOZ2 cells and BCNU-resistant SWOZ2（SWOZ2-BCNU） cells.The siRNA targeting to human 4E-BP1 mRNA was transfected into SWOZ2 cells.Cell counting kit-8 was used to detect the sensitivity of the cells to BCNU before and after transfection.The location of 4EBP1 and p-4E-BP1（T70） in SWOZ2 cells and SWOZ2-BCNU cells was observed by the method of immunofluorescence.RESULTS： The expression of 4E-BP1 in SWOZ2-BCNU cells was significantly lower than that in SWOZ2 cells.Down-regulation of 4E-BP1 expression in SWOZ2 cells decreased the sensitivity of the cells to BCNU.The expression of p-4E-BP1（T70） in the nucleus of SWOZ2-BCNU cells was significantly higher than that in the cytosol.CONCLUSION： 4E-BP1 is involved in human glioma acquired drug resistance as a translation key protein.

关 键 词：真核翻译起始因子4E结合蛋白1 神经胶质瘤 获得性耐药 

分 类 号：R363[医药卫生—病理学]