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首页> 外文期刊>British Journal of Cancer >Regulation by glutathione of drug transport in multidrug-resistant human lung tumour cell lines overexpressing multidrug resistance-associated protein
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Regulation by glutathione of drug transport in multidrug-resistant human lung tumour cell lines overexpressing multidrug resistance-associated protein

机译：谷胱甘肽对多药耐药的人肺肿瘤细胞株中过药耐药相关蛋白表达的调控

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Previous studies have shown that multidrug resistance (MDR) in the doxorubicin-selected lung tumour cell lines COR-L23/R, GLC4/ADR and MOR/R is associated with overexpression of the MRP gene. In this study we report that resistance to daunorubicin, vincristine and rhodamine 123 can be partially reversed in these cell lines by exposing the cells to buthionine sulphoximine (BSO), an inhibitor of glutathione (GSH) synthesis. This effect of BSO on drug resistance was associated with an increased intracellular accumulation of daunorubicin and rhodamine 123, owing to inhibition of the enhanced drug efflux. In contrast, the accumulation of daunorubicin was not increased by BSO treatment in a P-glycoprotein (P-gp)-mediated MDR cell line. BSO treatment (25 microM, 20 h) of the cell lines resulted in 60-80% depletion of cellular GSH levels. The effects of BSO on daunorubicin accumulation in the COR-L23/R and GLC4/ADR cells were associated with cellular GSH depletion. In addition, increase of cellular GSH levels in BSO-treated COR-L23/R and GLC4/ADR cells as a result of incubation with 5 mM GSH ethyl ester restored the accumulation deficit of daunorubicin. However, the transport of daunorubicin did not increase the GSH release in any of the cell lines. These results demonstrate that drug transport in MRP- but not in P-gp-overexpressing MDR tumour cell lines can be regulated by intracellular GSH levels.
机译：先前的研究表明，阿霉素选择的肺肿瘤细胞系COR-L23 / R，GLC4 / ADR和MOR / R中的多药耐药性（MDR）与MRP基因的过表达有关。在这项研究中，我们报道了将柔红霉素，长春新碱和若丹明123的抗性通过将细胞暴露于丁硫氨酸亚砜（BSO）（谷胱甘肽（GSH）合成的抑制剂）可以部分逆转。 BSO对耐药性的这种作用与柔红霉素和若丹明123的细胞内积累增加有关，这是由于抑制了增强的药物流出。相反，在P-糖蛋白（P-gp）介导的MDR细胞系中，BSO处理不会增加柔红霉素的积累。 BSO处理（25 microM，20 h）导致细胞GSH水平耗竭60-80％。 BSO对柔红霉素在COR-L23 / R和GLC4 / ADR细胞中积累的影响与细胞GSH耗竭有关。此外，与5 mM GSH乙酯孵育后，经BSO处理的COR-L23 / R和GLC4 / ADR细胞中细胞GSH含量的增加恢复了柔红霉素的积累不足。但是，柔红霉素的转运并未增加任何细胞系中GSH的释放。这些结果证明，在细胞内GSH水平可以调节药物在MRP表达而不在P-gp过表达的MDR肿瘤细胞系中的运输。

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