Lee W P, Lee C L, Kao M C
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Biochem Biophys Res Commun. 1992 Nov 30;189(1):92-100. doi: 10.1016/0006-291x(92)91530-4.
Two cell lines resistant to 0.1 microM vincristine (VCR) and 2.0 microM adriamycin (ADR), respectively, (designated HOB1/VCR0.1 and HOB1/ADR2.0) were established from a human immunoblastic B lymphoma cell line. These cell lines showed the typical MDR phenotype with overexpression of P-glycoprotein and decreased [3H]VCR accumulation. The retention amounts of intracellular [3H]VCR in these two cell lines could be augmented by verapamil. However, in spite of the overproduction of P-glycoprotein, both HOB1/VCR1.0 and HOB1/ADR2.0 cells did not exhibit decreased accumulation of intracellular [14C]ADR. And the retention of [14C]ADR was not affected by verapamil. Our data support that P-glycoprotein is a drug transporter more important for the development of drug resistance to VCR than to ADR.
分别从一株人免疫母细胞性B淋巴瘤细胞系建立了对0.1微摩尔长春新碱(VCR)和2.0微摩尔阿霉素(ADR)耐药的两株细胞系(命名为HOB1/VCR0.1和HOB1/ADR2.0)。这些细胞系表现出典型的多药耐药(MDR)表型,P-糖蛋白过表达且[3H]VCR蓄积减少。维拉帕米可增加这两株细胞系细胞内[3H]VCR的保留量。然而,尽管P-糖蛋白过量产生,HOB1/VCR1.0和HOB1/ADR2.0细胞均未表现出细胞内[14C]ADR蓄积减少。并且[14C]ADR的保留不受维拉帕米影响。我们的数据支持P-糖蛋白作为一种药物转运蛋白,对VCR耐药性发展的作用比对ADR更重要。