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Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P ‐glycoprotein
Author(s) -
Zandvliet M.,
Teske E.,
Chapuis T.,
FinkGremmels J.,
Schrickx J. A.
Publication year - 2013
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12039
Subject(s) - doxorubicin , canine lymphoma , multiple drug resistance , pharmacology , p glycoprotein , medicine , lymphoma , concomitant , tyrosine kinase inhibitor , tyrosine kinase , cancer research , oncology , drug resistance , chemotherapy , biology , cancer , receptor , microbiology and biotechnology
Overexpression of ABC ‐transporters including P gp, MRP 1, and BCRP has been associated with multidrug resistance ( MDR ) in both human and canine oncology. Therapeutic interventions to reverse MDR are limited, but include multidrug protocols and the temporary concomitant use of inhibitors of ABC ‐transporters. Recently, the use of tyrosine kinase inhibitors has been proposed to overcome MDR in human oncology. One of the tyrosine kinase inhibitors, masitinib, is licensed for veterinary use in the treatment of canine mast cell tumors. Therefore, this study aimed to assess the potential of masitinib to revert MDR in canine malignant lymphoma using an in vitro model with canine lymphoid cell lines. Masitinib had a mild antiproliferative effect on lymphoid cells, inhibited P gp function at concentrations equal to or exceeding 1 μ m and was able to reverse doxorubicin resistance. The current findings provide the rationale for a combined use of masitinib with doxorubicin in the treatment of dogs with doxorubicin‐resistant malignant lymphoma but await confirmation in clinical trials.