NDLI: Antiproliferative effects of masitinib and imatinib against canine oral fibrosarcoma in vitro

Content Provider	Springer Nature : BioMed Central
Author	Milovancev, Milan Helfand, Stuart C. Marley, Kevin Goodall, Cheri P. Löhr, Christiane V. Bracha, Shay
Abstract	Background Canine oral fibrosarcoma (COF) is one of the most common oral tumors in dogs and carries a guarded prognosis due to a lack of effective systemic therapeutic options. Mastinib and imatinib are two commonly used tyrosine kinase inhibitors (TKIs) in veterinary oncology but their potential efficacy against COF is uncharacterized. To begin investigating the rationale for use of these TKIs against COF, the present study tested for the presence TKI targets PDGFR-α, PDGFR-β, Kit, and VEGFR-2 and examined the in vitro effects on cell viability after TKI treatment alone or with doxorubicin. Immunohistochemistry for PDGFR-α, PDGFR-β, Kit, and VEGFR-2 was performed in 6 COF tumor biopsies. Presence of these same receptors within 2 COF cell lines was probed by reverse transcription-polymerase chain reaction and, for those with mRNA detected, confirmed via western blot. Effects on cell viability were assessed using an MTS assay after masitinib or imatinib treatment alone (0-100 μM), or in combination with doxorubicin (0-3000 nM doxorubicin). Anti-PDGFRB siRNA knockdown was performed and the effect on cell viability quantified. Results Expression of the TKI targets evaluated was similar between the 2 COF cell lines and the 6 COF tumor biopsies: PDGFR-α and PDGFR-β were detected in neoplastic cells from most COF tumor biopsies (5/6 and 6/6, respectively) and were present in both COF cell lines; KIT and KDR were not detected in any sample. Masitinib and imatinib IC50 values ranged from 7.9–33.4 μM, depending on the specific TKI and cell line tested. The addition of doxorubicin resulted in synergistic cytotoxicity with both TKIs. Anti-PDGFRB siRNA transfection reduced PDGFR-β protein expression by 77 % and 67 % and reduced cell viability by 24 % (p < 0.0001) and 28 % (0 = 0.0003) in the two cell lines, respectively. Conclusions These results provide rationale for further investigation into the use of TKIs, possibly in combination with doxorubicin, as treatment options for COF.
Related Links	https://bmcvetres.biomedcentral.com/counter/pdf/10.1186/s12917-016-0712-x.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	17466148
DOI	10.1186/s12917-016-0712-x
Journal	BMC Veterinary Research
Issue Number	1
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2016-06-04
Access Restriction	Open
Subject Keyword	Veterinary Medicine Veterinary Science Zoology Transgenics Dog Oral fibrosarcoma Masitinib Imatinib Platelet-derived growth factor receptor Veterinary Medicine/Veterinary Science
Content Type	Text
Resource Type	Article
Subject	Veterinary Medicine
Journal Impact Factor	2.3/2023
5-Year Journal Impact Factor	2.6/2023

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