title: In vitro effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine hemangiosarcoma cell lines.
abstract: 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.
authors.affiliation: Department of Small Animal Clinical Sciences, University of Florida, Gainesville, FL, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Lyles
authors.forename: R J
authors.initials: RJ
authors.lastname: Milner
authors.forename: K
authors.initials: K
authors.lastname: Kow
authors.forename: M E
authors.initials: ME
authors.lastname: Salute
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006394:Hemangiosarcoma / Q000188:drug therapy / Q000662:veterinary*; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D066298:In Vitro Techniques; D009383:Neoplasms, Vascular Tissue / Q000188:drug therapy / Q000662:veterinary*; D010880:Piperidines; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines; D012878:Skin Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D013844:Thiazoles / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010880:Piperidines; D011725:Pyridines; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D053148:Caspase 3; D053179:Caspase 7; C526575:masitinib