P型铜转运ATP酶(ATP7B)在肺腺癌细胞株A549中的表达与顺铂耐药的关系  

Expression of Copper-Transporting P-Type Adenosine Triphosphatase(ATP7B) Correlates with Cisplatin-Resistance in Human Lung Adenocarcinoma Cell Line A549

作　　者：高贵洲[1] 王建军[1] 石思恩[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胸外科,武汉430022

出　　处：《中国肺癌杂志》2009年第4期350-353,共4页Chinese Journal of Lung Cancer

摘　　要：背景与目的顺铂作为肺癌的基础化疗药物,顺铂耐药是导致肺癌患者化疗失败的重要原因。本实验通过检测P型铜转运ATP酶在肺腺癌细胞A549不同水平耐药株中的表达,以评估ATP7B与A549细胞顺铂耐药的关系。方法采用逐步增加顺铂剂量的方法,诱导出3株不同水平耐顺铂A549细胞株A549/DDP0.5、A549/DDP1.0、A549/DDP2.0,MTT方法检测各组别细胞对顺铂敏感性,应用RT-PCR及Western Blot方法分别检测各组别细胞的ATP7B的mRNA及蛋白表达水平,分析A549细胞顺铂敏感性与ATP7B表达水平的关系。结果相对于亲本A549细胞,3组耐药细胞的顺铂耐药指数分别达到了1.7、3.2、5.2(P<0.001),与此相对应ATP7B的mRNA表达水平分别达到了亲本A549细胞的1.6、4.9、10.1倍(P<0.001),同样地ATP7B的蛋白表达水平也呈现出与顺铂耐药性相平行的递增性高表达。结论肺腺癌细胞A549的顺铂耐药与细胞ATP7B高表达有关,后者的高表达有可能促成了A549细胞的获得性顺铂耐药。Background and objective Cisplatin is the basic chemotherapy agent of lung carcinoma, and cisplatin-resistance mostly leads to the failing of chemotherapy in the patients. The aim of this study is to investigate the relationship between the expression of copper-transporting P-type adenosine triphosphatase （ATPTB） and cisplatinresistance in different cisplatin-resistant A549 cells. Methods Three differently cisplatin-resistant A549 subliMes （A549/DDP0.5, A549/DDP1.0, A549/DDP2.0） were established from their parental human lung adenocarcinoma cell line A549 which was sensitive to cisplatin, by gradually increasing concentration of cisplatin. The resistance indexes of all the subliMes were checked by MTT method. The levels of ATP7B mRNA and protein were measured by RT-PCR and Western Blot respectively in all the cell lines. Results The resistance indexes of the three cisplatin-resistant subliMes were 1.7, 3.2 and 5.2 respectively （P〈0.001）, and the levels of ATP7B mRNA were 1.6, 4.9 and 10.1 folds compared to the parental A549 ceils （P〈0.001）. Meanwhile, expression of ATP7B protein was enhanced in the three cisplatin-resistant sulines corresponding to their cisplatin-resistance. Conclusion Expression of ATPTB correlates with cisplatin-resistance in A549 cells, and maybe ATPTB contributes to acquisition of cisplatin-resistance.

关 键 词：肺肿瘤 细胞系 耐药 顺铂 

分 类 号：R734.2[医药卫生—肿瘤]