<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec id="j_jvetres-2021-042_s_005">
<h3>Introduction</h3>
<p>Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action.</p></sec>
<sec id="j_jvetres-2021-042_s_006">
<h3>Material and Methods</h3>
<p>The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells.</p></sec>
<sec id="j_jvetres-2021-042_s_007">
<h3>Results</h3>
<p>Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC<sub>50</sub> of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells.</p></sec>
<sec id="j_jvetres-2021-042_s_008">
<h3>Conclusion</h3>
<p>In this study, masitinib suppressed cell proliferation concomitantly <italic>via</italic> induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells <italic>in vitro</italic>, suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.</p></sec>
</abstract>

Introduction
Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action.

Material and Methods
The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells.

Results
Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC50 of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells.

Conclusion
In this study, masitinib suppressed cell proliferation concomitantly via induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells in vitro, suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.

Effects of tyrosine kinase inhibitor-masitinib mesylate on canine mammary tumour cell lines

Journal of Veterinary Research

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Introduction
Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib...

Effects of tyrosine kinase inhibitor-masitinib mesylate on canine mammary tumour cell lines

Published Online: Jul 24, 2021

Page range: 351 - 359

Received: Feb 05, 2021

Accepted: Jul 05, 2021

DOI: https://doi.org/10.2478/jvetres-2021-042

Keywords
tyrosine kinase inhibitor, masitinib, canine mammary cancer, apoptosis, VEGF

© 2021 F. Ustun-Alkan et al. published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Effects of tyrosine kinase inhibitor-masitinib mesylate on canine mammary tumour cell lines

Published Online: Jul 24, 2021

Page range: 351 - 359

Received: Feb 05, 2021

Accepted: Jul 05, 2021

DOI: https://doi.org/10.2478/jvetres-2021-042

Keywordstyrosine kinase inhibitor, masitinib, canine mammary cancer, apoptosis, VEGF

© 2021 F. Ustun-Alkan et al. published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
tyrosine kinase inhibitor, masitinib, canine mammary cancer, apoptosis, VEGF