Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P-glycoprotein
Overexpression of ABC‐transporters including Pgp, MRP1, 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‐transpo...
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| Veröffentlicht in: | Journal of veterinary pharmacology and therapeutics 2013-12, Vol.36 (6), p.583-587 |
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| container_title | Journal of veterinary pharmacology and therapeutics |
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| creator | Zandvliet, M. Teske, E. Chapuis, T. Fink-Gremmels, J. Schrickx, J. A. |
| description | Overexpression of ABC‐transporters including Pgp, MRP1, 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 Pgp function at concentrations equal to or exceeding 1 μm 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. |
| doi_str_mv | 10.1111/jvp.12039 |
| format | Article |
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Masitinib had a mild antiproliferative effect on lymphoid cells, inhibited Pgp function at concentrations equal to or exceeding 1 μm and was able to reverse doxorubicin resistance. 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A.</creatorcontrib><title>Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P-glycoprotein</title><title>Journal of veterinary pharmacology and therapeutics</title><addtitle>J. Vet. Pharmacol. Ther</addtitle><description>Overexpression of ABC‐transporters including Pgp, MRP1, 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 Pgp function at concentrations equal to or exceeding 1 μm 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.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - genetics</subject><subject>ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Drug</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Fluoresceins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Rhodamine 123 - metabolism</subject><subject>Succinimides - metabolism</subject><subject>Thiazoles - pharmacology</subject><issn>0140-7783</issn><issn>1365-2885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1P3DAQhi3UCra0h_4B5CM9BPyRD-eIoIXCQqnUgtSLNXEmrCFrb-2Ekn9fbxe41ZeRPc-8Yz2EfOTsgKdzeP-4OuCCyXqLzLgsi0woVbwhM8ZzllWVkjvkXYz3jDGpON8mO0LKUgohZsRfQrSDdbahAR8xRIy09U8-jI011qXHaOMAziBNNwPOOqT9tFwtvG2pwb6PtJlSb2Gbdc4dHRZIu9GZwXpHfUevs7t-Mn4V_IDWvSdvO-gjfniuu-Tnl88_js-y-bfTr8dH88zkoq6zDqATojTQQiNkh1iIqhAttE2uEHgjGdYtEyXnBjsFNVeAQkKlBORcskLukv1Nbtr7e8Q46KWN6--CQz9GzfO8FqUqFUvopw1qgo8xYKdXwS4hTJozvfark1_9z29i955jx2aJ7Sv5IjQBhxvgj-1x-n-SPr-5fonMNhPJMz69TkB40GUlq0LfXp3q4ns9v_h1Uukz-ReQbJZr</recordid><startdate>201312</startdate><enddate>201312</enddate><creator>Zandvliet, M.</creator><creator>Teske, E.</creator><creator>Chapuis, T.</creator><creator>Fink-Gremmels, J.</creator><creator>Schrickx, J. 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Ther</addtitle><date>2013-12</date><risdate>2013</risdate><volume>36</volume><issue>6</issue><spage>583</spage><epage>587</epage><pages>583-587</pages><issn>0140-7783</issn><eissn>1365-2885</eissn><abstract>Overexpression of ABC‐transporters including Pgp, MRP1, 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. 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| ispartof | Journal of veterinary pharmacology and therapeutics, 2013-12, Vol.36 (6), p.583-587 |
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| subjects | Animals Antibiotics, Antineoplastic - pharmacology ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism Cell Line, Tumor Dogs Dose-Response Relationship, Drug Doxorubicin - pharmacology Drug Resistance, Neoplasm - drug effects Fluoresceins - metabolism Gene Expression Regulation Protein Kinase Inhibitors - pharmacology Rhodamine 123 - metabolism Succinimides - metabolism Thiazoles - pharmacology |
| title | Masitinib reverses doxorubicin resistance in canine lymphoid cells by inhibiting the function of P-glycoprotein |
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