title: Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma.
abstract: Canine lymphoma is routinely treated with a doxorubicin-based multidrug chemotherapy protocol, and although treatment is initially successful, tumor recurrence is common and associated with therapy resistance. Active efflux of chemotherapeutic agents by transporter proteins of the ATP-Binding Cassette superfamily forms an effective cellular defense mechanism and a high expression of these transporters is frequently observed in chemotherapy-resistant tumors in both humans and dogs. In this study we describe the ABC-transporter expression in a canine lymphoid cell line and a sub-cell line with acquired drug resistance following prolonged exposure to doxorubicin. This sub-cell line was more resistant to doxorubicin and vincristine, but not to prednisolone, and had a highly increased P-glycoprotein (P-gp/abcb1) expression and transport capacity for the P-gp model-substrate rhodamine123. Both resistance to doxorubicin and vincristine, and rhodamine123 transport capacity were fully reversed by the P-gp inhibitor PSC833. No changes were observed in the expression and function of the ABC-transporters MRP-1 and BCRP. It is concluded that GL-40 cells represent a useful model for studying P-gp dependent drug resistance in canine lymphoid neoplasia, and that this model can be used for screening substances as potential P-gp substrates and their capacity to modulate P-gp mediated drug resistance.
authors: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, P.O. Box 80154, 3508 TD Utrecht, The Netherlands. Electronic address: M.Zandvliet@uu.nl.
authors: M
authors: M
authors: Zandvliet
authors: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, P.O. Box 80154, 3508 TD Utrecht, The Netherlands.
authors: E
authors: E
authors: Teske
authors: IRAS Veterinary Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
authors: J A
authors: JA
authors: Schrickx
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D020112:Rhodamine 123 / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020112:Rhodamine 123
keywords: ABC-transporters; Canine lymphoma; In vitro; Multidrug-resistance model; P-glycoprotein