title: Drug resistance mechanisms and MRP expression in response to epirubicin treatment in a human leukaemia cell line.
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.
authors.affiliation: Bill Walsh Cancer Research Laboratories, Department of Clinical Oncology, Royal North Shore Hospital, St. Leonards, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Davey
authors.forename: T J
authors.initials: TJ
authors.lastname: Longhurst
authors.forename: M W
authors.initials: MW
authors.lastname: Davey
authors.forename: L
authors.initials: L
authors.lastname: Belov
authors.forename: R M
authors.initials: RM
authors.lastname: Harvie
authors.forename: D
authors.initials: D
authors.lastname: Hancox
authors.forename: H
authors.initials: H
authors.lastname: Wheeler
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D015251:Epirubicin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D019328:Buthionine Sulfoximine; D015251:Epirubicin; D008717:Methionine Sulfoximine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014700:Verapamil