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In vitro effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell lines
Author(s) -
Lyles S. E.,
Milner R. J.,
Kow K.,
Salute M. E.
Publication year - 2012
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/j.1476-5829.2012.00335.x
Subject(s) - mesylate , tyrosine kinase inhibitor , in vitro , pharmacology , cell culture , medicine , chemistry , cancer , biology , biochemistry , organic chemistry , genetics
This study evaluated the in vitro activity of masitinib mesylate against canine hemangiosarcoma ( HSA ) cell lines after treatment with increasing concentrations of masitinib mesylate (0.01–100 µM) for 24, 48 and 72 h. Results indicated that masitinib mesylate caused a dose‐ and time‐dependent decrease in HSA cell proliferation. The 50% inhibitory concentration ( IC 50 ) at 72 h for three HSA cell lines ( DEN , Fitz and SB ) was found to be 8.56, 9.41 and 10.65 µM, respectively. Further investigation demonstrated that masitinib mesylate induced apoptosis in all HSA cell lines, including activation of caspase‐3/7. Measurement of VEGF levels in cell supernatant found a statistically significant increased VEGF in close proximity to the IC 50 of each cell line followed by a decline back towards baseline. These findings indicate that masitinib mesylate causes dose‐dependent HSA cell death in vitro and supports future clinical trials of masitinib for canine HSA .