ABC-transporters; Canine lymphoma; In vitro; Multidrug-resistance model; P-glycoprotein
Abstract :
[en] 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.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Zandvliet, M.
Teske, Erik ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Dép. clinique des animaux de compagnie et des équidés (DCA)
Schrickx, J. A.
Language :
English
Title :
Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma.
Publication date :
2014
Journal title :
Toxicology in Vitro
ISSN :
0887-2333
eISSN :
1879-3177
Publisher :
Elsevier, Netherlands
Volume :
28
Issue :
8
Pages :
1498-506
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier Ltd. All rights reserved.
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