Marks D C, Davey M W, Davey R A, Kidman A D
Neurobiology Unit, School of Biological and Biomedical Sciences, University of Technology, Sydney, N.S.W., Australia.
Br J Haematol. 1993 May;84(1):83-9. doi: 10.1111/j.1365-2141.1993.tb03028.x.
The relationship between differentiation and P-glycoprotein expression in response to chemotherapeutic drugs was studied in the K562 human leukaemia cell line by treatment with low, but clinically achievable levels of vinblastine and epirubicin. Resistant sublines were easily generated with the multidrug resistant phenotype being expressed in response to drug treatment as low as 1 ng/ml vinblastine and 10 ng/ml epirubicin. These sublines showed stable but heterogeneous expression of P-glycoprotein as revealed by immunocytochemistry, and confirmed by cloning. This heterogeneity was maintained over 18 months with intermittent drug treatment. While selection for resistance induced erythroid and myeloid differentiation, expression of P-glycoprotein was not correlated with the stem cell antigen CD34 or with specific markers of erythroid or myeloid differentiation.
通过用低剂量但临床可达到水平的长春碱和表柔比星处理K562人白血病细胞系，研究了分化与化疗药物反应中P-糖蛋白表达之间的关系。低至1 ng/ml长春碱和10 ng/ml表柔比星的药物处理即可轻松产生具有多药耐药表型的耐药亚系。免疫细胞化学显示这些亚系表现出P-糖蛋白稳定但异质性的表达，并经克隆证实。通过间歇性药物处理，这种异质性在18个月内得以维持。虽然对耐药性的选择诱导了红系和髓系分化，但P-糖蛋白的表达与干细胞抗原CD34或红系或髓系分化的特异性标志物无关。
