Marks D C, Davey M W, Davey R A, Kidman A D
Neurobiology Unit, University of Technology, Sydney, NSW, Australia.
Biochem Pharmacol. 1995 Aug 8;50(4):475-80. doi: 10.1016/0006-2952(95)00157-u.
With the increasing use of inducers of cellular differentiation in the treatment of leukaemia, it is essential to understand the relationship between differentiation and the expression of the multidrug resistance. Using the K562 human leukaemia cell line and its multidrug resistant subline K562/E15B, differentiation was examined along two different pathways, megakaryocyte in response to treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), and erythroid in response to treatment with sodium butyrate, in the same cell line. P-glycoprotein expression was increased in the multidrug resistant K562/E15B subline, but not induced in the parental K562 cell line. However, both treatments conferred a different phenotype on the drug resistant subline. TPA treatment caused an increase in P-glycoprotein, increased drug resistance and decreased rhodamine-123 accumulation which was verapamil sensitive, demonstrating that TPA induced a fully functional P-glycoprotein. However, sodium butyrate treatment caused an increase in P-glycoprotein without increased drug resistance or without decreased rhodamine-123 accumulation suggesting that the P-glycoprotein induced by sodium butyrate was nonfunctional. These results stress the importance of examining not only the expression of P-glycoprotein in cells, but also the function of the P-glycoprotein induced.
随着细胞分化诱导剂在白血病治疗中的应用日益增加，了解分化与多药耐药性表达之间的关系至关重要。利用K562人白血病细胞系及其多药耐药亚系K562/E15B，在同一细胞系中沿着两条不同途径检测分化情况，即使用12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）处理诱导向巨核细胞分化，以及使用丁酸钠处理诱导向红细胞分化。P - 糖蛋白在多药耐药的K562/E15B亚系中表达增加，但在亲代K562细胞系中未被诱导。然而，两种处理都赋予了耐药亚系不同的表型。TPA处理导致P - 糖蛋白增加、耐药性增强以及罗丹明 - 123积累减少，且该减少对维拉帕米敏感，表明TPA诱导出了功能完全的P - 糖蛋白。然而，丁酸钠处理导致P - 糖蛋白增加，但耐药性未增强且罗丹明 - 123积累未减少，这表明丁酸钠诱导的P - 糖蛋白无功能。这些结果强调了不仅要检测细胞中P - 糖蛋白的表达，还要检测所诱导的P - 糖蛋白功能的重要性。
