Davey R A, Longhurst T J, Davey M W, Belov L, Harvie R M, Hancox D, Wheeler H
Bill Walsh Cancer Research Laboratories, Department of Clinical Oncology, Royal North Shore Hospital, St. Leonards, Australia.
Leuk Res. 1995 Apr;19(4):275-82. doi: 10.1016/0145-2126(94)00159-8.
A drug resistant series of sublines were developed by treating the human leukaemia CCRF-CEM cell line with 16-1000 ng/ml of the anthracycline, epirubicin. The sublines developed resistance in two stages, neither involving detectable levels of P-glycoprotein. Treatment with up to 50 ng/ml epirubicin produced sublines with cross resistance limited to the anthracyclines and etoposide. Treatment with 100-1000 ng/ml epirubicin produced sublines with increased expression of the mrp gene, increased resistance to the anthracyclines and etoposide, additional cross resistance to vincristine and colchicine, decreased drug accumulation and reversal of resistance by verapamil and by buthionine sulphoximine (BSO; an inhibitor of glutathione synthesis). Our results indicate an interaction between MRP and glutathione metabolism as a mechanism for multidrug resistance.
通过用16 - 1000纳克/毫升的蒽环类药物表柔比星处理人白血病CCRF - CEM细胞系，建立了一系列耐药亚系。这些亚系分两个阶段产生耐药性，均未涉及可检测水平的P - 糖蛋白。用高达50纳克/毫升的表柔比星处理产生的亚系具有仅限于蒽环类药物和依托泊苷的交叉耐药性。用100 - 1000纳克/毫升的表柔比星处理产生的亚系，其mrp基因表达增加，对蒽环类药物和依托泊苷的耐药性增加，对长春新碱和秋水仙碱有额外的交叉耐药性，药物蓄积减少，维拉帕米和丁硫氨酸亚砜胺（BSO；谷胱甘肽合成抑制剂）可逆转耐药性。我们的结果表明MRP与谷胱甘肽代谢之间的相互作用是多药耐药的一种机制。
