多药耐药相关蛋白基因在非小细胞肺癌中的表达

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探讨多药耐药相关蛋白(MRP)基因表达与非小细胞肺癌(NSCLC)多药耐药(MDR)发生的关系。采用半定量逆转录多聚酶链反应(RTPCR)和免疫组织化学染色方法,结合体外化疗药敏实验,检测32例NSCLC中MRP基因表达水平和对9种化疗药物敏感性。结果:NSCLC中MRPmRNA表达阳性率为71.9%,癌旁肺组织中为10%;MRP蛋白表达阳性率为65.6%,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~高分化癌中MRPmRNA和蛋白表达明显高于低分化癌(P<0.05);NSCLC中MRPmRNA表达和MRP蛋白表达呈正相关(r=0.97,P=0.0001)。NSCLC中对长春新碱、足叶乙甙和阿霉素耐药组,其MRP蛋白表达率明显高于敏感组(P<0.05)。表明MRP基因表达是非小细胞肺癌原发性多药耐药的重要参与因素,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,MRP基因检测和体外化疗药敏实验对进一步阐明肺癌耐药机理有重要意义 To investigate the relationship between multidrug resistance-associated protein (MRP) gene expression and multidrug resistance (MDR) in non-small cell lung cancer (NSCLC). Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining methods were combined with in vitro chemotherapy sensitivity test to detect the expression level of MRP gene and sensitivity to 9 kinds of chemotherapy drugs in 32 cases of NSCLC. Results: The positive rate of MRP mRNA expression was 71.9% in NSCLC and 10% in para-tumor lung tissue. The positive rate of MRP protein expression was 65.6%. It was expressed both in the membrane and cytoplasm of tumor cells. No expression was detected in tissues; MRP mRNA and protein expression was significantly higher in moderately to well-differentiated carcinomas than in poorly differentiated carcinomas (P<0.05); MRP mRNA expression was positively correlated with MRP protein expression in NSCLC (r=0.97, P=0. .0001). The expression of MRP protein in NSCLC resistant to vincristine, etoposide and adriamycin was significantly higher than that in the sensitive group (P<0.05). It indicates that MRP gene expression is an important factor in the primary multidrug resistance of non-small cell lung cancer. Its overexpression is regulated by transcriptional and translational levels. NSCLC is resistant to vincristine, etoposide and adriamycin. The important reason is that MRP protein expression, MRP gene detection and in vitro chemotherapy susceptibility testing are important for further elucidating the drug resistance mechanism of lung cancer.
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