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染料木黄酮及相关化合物对MRP介导的罗丹明123外排的促进作用。

Acceleration of MRP-associated efflux of rhodamine 123 by genistein and related compounds.

作者信息

Versantvoort C H, Rhodes T, Twentyman P R

机构信息

Medical Research Council, Clinical Oncology and Radiotherapeutics Unit, Cambridge, UK.

出版信息

Br J Cancer. 1996 Dec;74(12):1949-54. doi: 10.1038/bjc.1996.658.

DOI:10.1038/bjc.1996.658
PMID:8980395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2074826/
Abstract

Multidrug resistance (MDR), caused by overexpression of either P-glycoprotein or the multidrug resistance protein (MRP), is characterised by a decreased cellular drug accumulation due to an enhanced drug efflux. In this study, we examined the effects of genistein and structurally related (iso)flavonoids on the transport of rhodamine 123 (Rh123) and daunorubicin in the MRP-overexpressing MDR lung cancer cell lines COR-L23/R and MOR/R. Genistein, genistin, daidzein and quercetin showed major differences in effects on Rh123 vs daunorubicin transport in the MRP-mediated MDR cell lines: the accumulation of daunorubicin was increased, whereas the accumulation of Rh123 was decreased by the flavonoids. The depolarisation of the membrane potential caused by genistein might be involved in the acceleration of the efflux of Rh123 measured in the MRP-overexpressing cell lines. These observations should be taken into account when using fluorescent dyes as probes for determination of transporter activity as a measure of MDR.

摘要

多药耐药性（MDR）由P-糖蛋白或多药耐药蛋白（MRP）的过度表达引起，其特征是由于药物外排增强导致细胞内药物蓄积减少。在本研究中，我们检测了染料木黄酮及结构相关的（异）黄酮对过表达MRP的多药耐药肺癌细胞系COR-L23/R和MOR/R中罗丹明123（Rh123）和柔红霉素转运的影响。染料木黄酮、染料木苷、大豆苷元和槲皮素对MRP介导的多药耐药细胞系中Rh123与柔红霉素转运的影响存在主要差异：黄酮类化合物使柔红霉素的蓄积增加，而使Rh123的蓄积减少。染料木黄酮引起的膜电位去极化可能与过表达MRP的细胞系中检测到的Rh123外排加速有关。在使用荧光染料作为测定转运蛋白活性以衡量多药耐药性的探针时，应考虑这些观察结果。

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