非小细胞肺癌患者耐多药相关蛋白基因的表达

Expression of multidrug resistanceassociated protein gene in nonsmall cell lung cancer

目的探讨耐多药相关蛋白（ＭＲＰ）基因表达与非小细胞肺癌（ＮＳＣＬＣ）耐多药（ＭＤＲ）发生的关系。方法采用逆转录聚合酶链反应（ＲＴＰＣＲ）和免疫组织化学染色方法，结合体外化疗药敏试验，检测３２例ＮＳＣＬＣ患者ＭＲＰ基因表达水平和对９种化疗药物敏感性。结果ＮＳＣＬＣ癌组织中ＭＲＰｍＲＮＡ表达阳性率为７２％，癌旁肺组织中为１０％；癌组织中ＭＲＰ蛋白表达阳性率为６６％，在肿瘤细胞胞膜和胞浆内均有表达，癌旁肺组织中未见表达；中、高分化癌组织中ＭＲＰｍＲＮＡ和蛋白表达明显高于低分化癌（Ｐ＜０．０５）；ＮＳＣＬＣ患者ＭＲＰｍＲＮＡ表达和ＭＲＰ蛋白表达呈正相关；ＮＳＣＬＣ患者对长春新碱、足叶乙甙和阿霉素耐药者，其ＭＲＰ蛋白表达率高于敏感者（Ｐ＜０．０５）。结论ＭＲＰ基因表达是引起ＮＳＣＬＣ原发性耐药的重要机制，它的过度表达通过转录水平和翻译水平调节实现，ＮＳＣＬＣ对长春新碱、足叶乙甙和阿霉素耐药的重要原因是ＭＲＰ蛋白表达。

Objective To study the relationship between expression of multidrug resistanceassociated protein (MRP) gene and occurrence of multidrug resistance (MDR) in nonsmall cell lung cancer (NSCLC). Methods Thirtytwo NSCLC samples were detected expression of MRP gene and chemosensitivity to 9 antitumor agents by RTPCR, immunohistochemistry method and in vitro chemosensitivity assay. Results The positive expression rate of MRP mRNA in NSCLC was 72%, in lung tissue near carcinoma was 10%; the positive expression rate of MRP in NSCLC was 66%, positive staining of MRP located in membrane and cytoplasm of tumor cells, but no positive staining in lung tissue; MRP mRNA and MRP expression of moderate to high differentiation carcinoma was significantly higher than that of low differentiation carcinoma (P<0.05). There was significant correlation between expression of MRP mRNA and MRP in NSCLC. The expression of MRP in NSCLC, which was resistant to vincristine, etoposide and adriamycin, was higher than that being sensitive to these drugs (P<0.05). Conclusions MRP gene may play an important role of intrinsic drug resistance in NSCLC, overexpression of MRP gene can be achieved through modulation at transcriptional and/or translational level. Overexpression of MRP is a major cause of resistance to vincristine, etoposide and adriamycin.