膀胱癌における抗癌剤投与によるMDR1遺伝子発現誘導の解析

Abstract

1)膀胱癌において抗癌剤が投与された治療群は未治療群に比べ, 有意に高いmultidrug resistant 1(MDR1)mRNA発現レベルを示した. 2)膀胱癌14例におけるneoajuvant動注化学療法前後の比較でも, 投与後に有意に高いMDR1mRNA発現レベルを認めた. 3)抗癌剤投与により膀胱癌のMDR1遺伝子発現が誘導されることが示唆された

Using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based quantitative analysis method, we investigated MDR1 mRNA expression levels in 58 bladder cancer specimens to determine whether MDR1 gene expression was induced or enhanced in bladder cancers during chemotherapy. In bladder cancer specimens which were obtained from patients treated with anticancer drugs, significantly higher expression levels of MDR1 mRNA were observed than in those from patients not treated with any anticancer drugs (p = 0.0134, Mann-Whitney U test). From 14 patients who had bladder cancer, clinical specimens were obtained before and after neoadjuvant intra-arterial chemotherapy. The expression levels of MDR1 mRNA were significantly higher in the post-treatment specimens than in the pre-treatment specimens (p = 0.0298, Wilcoxon signed-rank test). Of these 14 patients, 7 patients exhibited increased levels of MDR1 mRNA expression after chemotherapy. In 6 patients, there were no changes in the MDR1 mRNA expression levels before and after chemotherapy. Only one patient exhibited decreased levels of MDR1 mRNA expression after chemotherapy. No significant correlations were observed, between MDR1 mRNA expression levels and effect of the chemotherapy determined microscopically, dosage of anticancer drugs, or patient outcome. In conclusion, this study indicates that MDR1 gene expression in bladder cancers is induced and enhanced during chemotherapy. This overexpression of the MDR1 gene may contribute to resistance to anticancer drugs after repeated chemotherapy.