McGrath T, Center M S
Biochem Biophys Res Commun. 1987 Jun 30;145(3):1171-6. doi: 10.1016/0006-291x(87)91560-9.
Previous studies have shown that the development of multi-drug resistance in cell lines treated with chemotherapeutic agents is closely associated with the overexpression of a 170-180 kilodalton surface membrane glycoprotein (P-glycoprotein). In the present study a monoclonal antibody against the P-glycoprotein was used to determine if this protein is overexpressed in multi-drug resistant HL60 cells. Using either indirect immunofluorescent staining or immunoblot analysis P-glycoprotein could not be detected in HL60 cells isolated for resistance to adriamycin. In contrast HL60 cells isolated for resistance to vincristine contain the P-glycoprotein and the amount of this material increases with increasing levels of resistance. These studies thus demonstrate adriamycin resistance in P-glycoprotein negative HL60 cells. Furthermore adriamycin and vincristine are found to have distinct effects in inducing overexpression of P-glycoprotein in the HL60 cell line. This information could be useful in the development of therapeutic strategies for the treatment of certain forms of cancer.
先前的研究表明,用化疗药物处理的细胞系中多药耐药性的产生与一种170 - 180千道尔顿的表面膜糖蛋白(P - 糖蛋白)的过度表达密切相关。在本研究中,使用一种针对P - 糖蛋白的单克隆抗体来确定该蛋白在多药耐药的HL60细胞中是否过度表达。通过间接免疫荧光染色或免疫印迹分析,在对阿霉素耐药的HL60细胞中均未检测到P - 糖蛋白。相比之下,对长春新碱耐药的HL60细胞含有P - 糖蛋白,并且这种物质的量随着耐药水平的增加而增加。因此,这些研究证明了P - 糖蛋白阴性的HL60细胞对阿霉素耐药。此外,发现阿霉素和长春新碱在诱导HL60细胞系中P - 糖蛋白过度表达方面具有不同的作用。这一信息可能有助于制定治疗某些癌症形式的治疗策略。