Up-regulation of MRP4 and down-regulation of influx transporters in human leukemic cells with acquired resistance to 6-mercaptopurine
Up-regulation of MRP4 and down-regulation of influx transporters in human leukemic cells with acquired resistance to 6-mercaptopurine
复制标题
对 6-巯基嘌呤获得性耐药的人白血病细胞中 MRP4 的上调和流入转运蛋白的下调
DOI：
10.1016/j.leukres.2007.09.015
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发表时间：
2008-05-01
影响因子：
2.7
通讯作者：
Chen, Zhe-Sheng
中科院分区：
文献类型：
--
作者：
Peng, Xing-Xiang;Shi, Zhi;Chen, Zhe-Sheng
为了探讨细胞对6-MP耐药的机制，我们通过对人T淋巴细胞白血病细胞系(CEM)的逐步筛选，建立了一个耐6-MP的细胞系(CEM-MP5)。与亲本CEM细胞相比，CENI-MP5细胞对6-MP的抗性约为100倍。Western印迹分析显示CEM-MP5细胞多药耐药蛋白4(MRP4)表达增加，核苷转运蛋白hENT1、hCNT2和hCNT3表达水平降低。在CEM-MP5细胞中，[C-14]6-MP和/或其代谢物的积累减少，ATP依赖的外排增加，与外排泵的运行一致。综上所述，这些结果表明MRP4的上调和内流转运体的下调在CEM-MP5细胞对6-MP的耐药中起主要作用。(C)2007爱思唯尔有限公司。保留所有权利。
To investigate the mechanism of cellular resistance to 6-MP, we established a 6-MP resistant cell line (CEM-MP5) by stepwise selection of the human T-lymphoblastic leukemia cell line (CEM). CENI-MP5 cells were about 100-fold resistant to 6-MP compared with parental CEM cells. Western blot analysis demonstrated that multidrug resistant protein 4 (MRP4) was increased in CEM-MP5 cells, whereas the levels of the nucleoside transporters hENT1, hCNT2 and hCNT3 were decreased compared with those of parental CEM cells. Consistent with the operation of an efflux pump, accumulation of [C-14]6-MP and/or its metabolites was reduced, and ATP-dependent efflux was increased in CEM-MP5 cells. Taken together these results showed that up-regulation of MRP4 and down-regulation of influx transporters played a major role in 6-MP resistance of CEM-MP5 cells. (C) 2007 Elsevier Ltd. All rights reserved.