非小细胞肺癌细胞MRP1表达及其与耐顺铂关系的研究

Expression of MRP1 in human NSCLC tissues and its relationship with resistance to DDP

目的:研究多药耐药相关蛋白1(MRP1)是否在耐顺铂(DDP)的非小细胞肺癌(NSCLC)A549/DDP中高表达,探讨MRP1与NSCLC耐DDP的关系。方法:培养来源于同一母系的2株细胞系A549细胞系和A549/DDP细胞系,采用MTT法绘制A549细胞和A549/DDP细胞的生长曲线,分别计算A549细胞和A549/DDP细胞的耐药指数;应用RT-PCR检测A549细胞和A549/DDP细胞中MRP1 mRNA的表达水平。结果:A549及A549/DDP的半数抑制浓度分别为0.65μg/mL和3.7μg/mL,得出A549/DDP对DDP的耐药性是A549的5.5倍。A549/DDP中MRP1的在转录水平的表达显著高于A549中MRP1的表达,P<0.05。结论:MRP1在耐DDP的NSCLC中高表达,而在不耐DDP的NSCLC中低表达,甚至不表达,说明MRP1的高表达与肺癌耐DDP有关,为以后研究通过抑制MRP1的表达从而逆转肺癌耐DDP提供理论依据。

OBJECTIVE： To observe the expression of multidrug resistance-associated protein 1（MRP1） in the human NSCLC cell line A549 with resistance to cisplatin（A549/DDP）,so as to investigate the relationship between MRP1 and the human NSCLC cell with resistance to DDP.METHODS： Cultured two cell lines of A549 and A549/DDP which were from the same uterine.The growth curves of the two cell lines were drawn and their chemoresistance indexes were measured by methyl tetrazolium（MTT） assay.The expression levels of MRP1 mRMA in the two cell lines were observed by reverse transcription polymerase chain reaction（RT-PCR）.RESULTS： The chemoresistance index for A549 and A549/DDP were 0.65 μg/mL and 3.7 μg/mL,respectively.As a result,the resistance of A549/DDP to DDP was 5.5-fold greater than that of A549,and the expression of MRP1 was significantly up-regulated in A549/DDP（P0.05）.CONCLUSIONS： The expression of MRP1 in A549/DDP was up-regulated,whereas was down-regulated or none in A549.It shows that the overexpression of MRP1 has relation to the human lung cell with resistance to DDP,and provides the theory basis for reversing the sensitivity of DDP by decreasing the transcription of MRP1 mRNA.