Increased expression of multidrug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorubicin
Increased expression of multidrug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorubicin
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DOI：
10.1002/ijc.10246
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发表时间：
2002-04-01
影响因子：
6.4
通讯作者：
Naito, S
中科院分区：
文献类型：
--
作者：
Tada, Y;Wada, M;Naito, S
P-糖蛋白/多药耐药1（MDR1）和多药耐药蛋白1（MRP1）基因的过度表达与多种恶性肿瘤的临床结果密切相关，并且参与包括阿霉素在内的一些抗癌化疗药物的反应。已鉴定出六种与 MRP1 结构相似的人类 MRP 亚家族成员 (MRP2-7)。最近，一些癌细胞的MRP2和MRP3表达水平与阿霉素药物敏感性之间的关系已被报道，但临床样本与药物敏感性之间的关系仍不清楚。我们在临床过程中测定了膀胱癌中 MDR1、MRP1、MRP2 和 MRP3 基因的表达，并试图了解这些表达是否与阿霉素的药物反应相关。阿霉素用于化疗，包括膀胱内化疗和全身化疗，是治疗膀胱癌的重要抗癌药物。我们的研究使用定量逆转录酶聚合酶链反应 (RT-PCR) 分析，并使用体外琥珀酸脱氢酶抑制试验确定膀胱癌对阿霉素的敏感性。使用 47 个膀胱癌临床样本，我们证实了 MDR1、MRP1 和 MRP3 mRNA 水平与阿霉素耐药性的显着相关性。我们发现化疗后复发肿瘤和残留肿瘤中MDR1、MRP1、MRP2和MRP3的表达高于未治疗的原发肿瘤。特别是，残留肿瘤中的MDR1表达比未经治疗的原发肿瘤高5.7倍。 (C) 2002 Wiley-Liss, Inc.
Overexpression of the P-glycoprotein/multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1) gene is closely associated with the clinical outcome of various malignancies, and it is involved in responses to some anticancer chemotherapeutic agents including doxorubicin. Six human MRP subfamily members (MRP2-7) with structural similarities to MRP1 have been identified. Recently, the relationships between MRP2 and MRP3 expression levels of some cancer cells and drug sensitivity to doxorubicin have been reported, but the relationship between the clinical samples and drug sensitivity remains unclear. We determined the expressions of the MDR1, MRP1, MRP2 and MRP3 gene in bladder cancer during the clinical course and sought to learn whether the expression was correlated with drug responses to doxorubicin. Doxorubicin, used in chemotherapeutic treatment including intravesical and systemic chemotherapy, is an important anticancer agent for the treatment of bladder cancer. We used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for our study, and the sensitivity to doxorubicin in bladder cancer was determined using the in vitro succinate dehydrogenase inhibition test. Using 47 clinical samples of bladder cancer, we confirmed the significant correlation of MDR1, MRP1 and MRP3 mRNA levels with resistance to doxorubicin. We showed that the expression of MDR1, MRP1, MRP2 and MRP3 in recurrent tumors and residual tumors after chemotherapeutic treatment was higher than that in untreated primary tumors. In particular, the MDR1 expression in residual tumors was 5.7-fold higher than that in untreated primary tumors. (C) 2002 Wiley-Liss, Inc.