Elsevier

Leukemia Research

Volume 19, Issue 4, April 1995, Pages 275-282
Leukemia Research

Original article
Drug resistance mechanisms and MRP expression in response to epirubicin treatment in a human leukaemia cell line

https://doi.org/10.1016/0145-2126(94)00159-8Get rights and content

Abstract

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.

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    Present address: Peptide Technology, CSIRO, North Ryde 2113, Australia.

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