Roy S, Kenny E, Kennedy S, Larkin A, Ballot J, Perez De Villarreal M, Crown J, O'Driscoll L
St. Vincent's University Hospital, Dublin 4, Ireland.
Anticancer Res. 2007 May-Jun;27(3A):1325-30.
Multiple drug resistance (MDR), both inherent and acquired, is a serious problem in non-small cell lung carcinomas (NSCLC). The purpose of this study was to investigate the prevalence of expression of genes encoding drug efflux pumps, MDR1 and MRP-1, at both the mRNA and protein levels, in this type of cancer.
Tumour specimens (38 cases) were analysed using immunohistochemistry and, where possible (30 cases), also using reverse-transcriptase polymerase chain reaction.
The results from this analysis indicated that either, or both, drug efflux pumps were frequently expressed in NSCLC. Expression of mrp1 was found to be predominant over mdr1 at the mRNA level, while MDR1 P-gp was more frequently detected than MRP-1 protein. In some cases, proteins encoding pumps were detected without corresponding mRNAs--possibly due to differing sensitivities of the analysis techniques.
Future studies of mdr1 and mrp1 using increased-sensitivity qPCR techniques, in parallel with protein analysis, in larger cohorts of cases may help to elucidate the role of drug efflux pumps in NSCLC multiple drug resistance.
固有和获得性多药耐药(MDR)是非小细胞肺癌(NSCLC)中的一个严重问题。本研究的目的是调查在这类癌症中,编码药物外排泵MDR1和MRP - 1的基因在mRNA和蛋白质水平的表达情况。
使用免疫组织化学对38例肿瘤标本进行分析,并且在可能的情况下(30例),还使用逆转录聚合酶链反应进行分析。
该分析结果表明,药物外排泵中的一种或两种在NSCLC中经常表达。发现在mRNA水平上,mrp1的表达比mdr1占优势,而MDR1 P - gp比MRP - 1蛋白更频繁地被检测到。在某些情况下,检测到编码泵的蛋白质但没有相应的mRNA,这可能是由于分析技术的敏感性不同。
未来在更大病例队列中,使用灵敏度更高的定量PCR技术并结合蛋白质分析对mdr1和mrp1进行研究,可能有助于阐明药物外排泵在NSCLC多药耐药中的作用。