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首页> 外文期刊>Anti-cancer drugs >Sequential gene expression of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and lung resistance protein: functional activity of P-gp and MRP present in the doxorubicin-resistant human K562 cell lines.
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Sequential gene expression of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and lung resistance protein: functional activity of P-gp and MRP present in the doxorubicin-resistant human K562 cell lines.

机译：P-糖蛋白（P-gp），多药耐药相关蛋白（MRP）和肺耐药蛋白的顺序基因表达：阿霉素抗性人K562细胞系中P-gp和MRP的功能活性。

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摘要

Previous studies have reported that P-glycoprotein (P-gp), a transmembrane efflux pump involved in multidrug resistance (MDR), was overexpressed in the doxorubicin (Dox)-resistant human erythroleukemia cell line K562. Nevertheless, several results suggested that P-gp was not the only mechanism involved in these resistant cells. Sequential co-expression of other MDR-associated proteins was sometimes reported, as MDR-associated protein (MRP) and lung resistance protein (LRP), in different MDR cell lines. Thus, mRNA expression and stability of P-gp, MRP and LRP were analyzed, while their corresponding protein levels were quantified in correlation with functional assay, in the K562 cell line and two Dox-resistant variants (K562/R). Their P-gp content was in accordance with their degree of resistance, but not as much in the level of mRNA expression, suggesting a post-transcriptional regulation. On the other hand, MRP could play a minor role in MDR because of an unchanged expression in K562/R sublines. A surprising progressive disappearance of LRP in both resistant cells suggested that the original mechanism of drug redistribution may be operative, involving a negative role for LRP.
机译：先前的研究报道，参与多药耐药性（MDR）的跨膜外排泵P-糖蛋白（P-gp）在耐阿霉素（Dox）的人红白血病细胞系K562中过表达。然而，一些结果表明，P-gp不是这些抗性细胞参与的唯一机制。有时还报道了在不同的MDR细胞系中，与MDR相关蛋白（MRP）和肺耐药蛋白（LRP）顺序共表达其他与MDR相关的蛋白。因此，分析了K562细胞系和两个Dox耐药变体（K562 / R）中P-gp，MRP和LRP的mRNA表达和稳定性，同时定量了它们与功能测定相关的相应蛋白质水平。它们的P-gp含量与其抗性程度相对应，但在mRNA表达水平上却不尽相同，表明转录后调控。另一方面，由于K562 / R子系中的表达未发生变化，因此MRP在MDR中的作用很小。 LRP在这两个耐药细胞中令人惊讶地逐渐消失，表明药物重新分配的原始机制可能是有效的，对LRP起到了消极作用。

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