ABCB1 polymorphism as a predictive biomarker for amrubicin-induced neutropenia.
ABCB1 polymorphism as a predictive biomarker for amrubicin-induced neutropenia.
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ABCB1 多态性作为氨柔比星诱导的中性粒细胞减少症的预测生物标志物。
DOI：
10.1007/s00280-015-2723-x
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发表时间：
2014
期刊：
影响因子：
2
通讯作者：
Niimi A.
中科院分区：
文献类型：
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作者：
Takakuwa O;Oguri T;Uemura T;Kunii E;Nakao M;Hijikata H;Kawaguchi Y;Ohkubo H;Takemura M;Maeno K;Niimi A.
目的本研究的目的是确定是否有机阳离子转运蛋白（OCT）可以介导铂的摄取，以及OCT下调是否赋予对顺铂（CDDP）的耐药在cancer.MethodsTwo肺癌细胞系，PC-6和PC-14，及其耐药衍生物，PC-6/CDDP和PC-14/CDDP，进行了分析。OCT表达水平采用定量RT-PCR和Western印迹法测定。此外，OCT 6过表达的效果，诱导通过转染的OCT 6基因SLC 22 A16使用强制表达载体，对细胞的敏感性CDDP和细胞内铂积累进行了测量使用PC-14/CDDP cells. ResultsOCT 6的基因和蛋白质的表达下降，在两个CDDP耐药细胞系相比，他们在各自的亲本细胞的表达。与亲本细胞相比，经CDDP处理后，PC-14/CDDP细胞中铂的细胞内积聚减少。结论OCT 6是肺癌细胞摄取铂的重要介质，其表达下调可能是肺癌顺铂耐药的机制之一。
PurposeThe purposes of this study were to determine whether organic cation transporters (OCTs) can mediate platinum uptake, and whether OCT down-regulation confers resistance against cisplatin (CDDP) in cancer cells.MethodsTwo lung cancer cell lines, PC-6 and PC-14, and their CDDP-resistant derivatives, PC-6/CDDP and PC-14/CDDP, were analyzed. OCT expression levels were assayed using quantitative RT-PCR and Western blotting. Additionally, the effect of OCT6 overexpression, induced by transfection of the OCT6 geneSLC22A16using a forced expression vector, on cellular sensitivity to CDDP and on intracellular platinum accumulation was measured using PC-14/CDDP cells.ResultsBoth gene and protein expression of OCT6 were decreased in both CDDP-resistant cell lines compared with their expression in their respective parental cells. Intracellular accumulation of platinum was decreased in PC-14/CDDP cells compared with the parental cells after CDDP treatment. Furthermore, OCT6 overexpression induced by transfection of the OCT6 gene (SLC22A16) forced expression vector-sensitized PC-14/CDDP cells to CDDP and oxaliplatin (L-OHP) concomitant with increased intracellular concentration of platinum.ConclusionOCT6 is a mediator of platinum uptake in cancer cells, and down-regulation of OCT6 is possibly one of the mechanisms of resistance against cisplatin in lung cancer.