Details

Autor(en) / Beteiligte

• Fisher, C.J.
• Lejeune, A.T.
• Dark, M.J.
• Hernandez, O.M.
• Shiomitsu, K.

Titel

Evaluation of ponatinib in vitro effect in three canine mast cell tumor cell lines expressing FGFR-1, PDGFR-α, and VEGFR-2

Ist Teil von

• The veterinary journal (1997), 2021-03, Vol.269, p.105621-105621, Article 105621

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• •FGFR-1, PDGFR-α, and VEGFR-2 were expressed in all three mast cell tumor cell lines.•Ponatinib induced cytotoxicity on three canine mast cell tumor cell lines.•Ponatinib is a candidate of novel chemotherapeutic drug for canine mast cell tumors. Ponatinib is a broad-spectrum tyrosine kinase inhibitor that targets numerous receptor tyrosine kinases (RTKs), including but not limited to fibroblast growth factor receptor (FGFR)-1, platelet derived growth factor receptor (PDGFR)-α, and vascular endothelial growth factor receptor (VEGFR)-2. This study evaluated the expression of FGFR-1, PDGFR-α, and VEGFR-2 in three canine mast cell tumor (MCT) cell lines (CM-MC1, VI-MC1, CoMS) and the effects of ponatinib on these MCT cell lines. Quantitative RT-PCR confirmed the expression of FGFR-1, PDGFR-α, and VEGFR-2 in the three MCT cell lines. Ponatinib exhibited dose- and time-dependent cytotoxicity in MCT cell lines via MTT assay. The IC50 for 24, 48, and 72 h across the three cell lines ranged from 38.47 nM to 103.3 nM, which is clinically comparable to dose ranges established for humans. Significantly increased apoptosis in each cell line was seen between 12 and 18 h after treatment with IC50 of ponatinib via Annexin-V and Caspase-3/7 assays. These data suggest that ponatinib could be a possible therapeutic agent for canine MCTs. Further studies are needed to investigate the prognostic value of FGFR-1, PDGFR-α, and VEGFR-2 in canine MCTs.