Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2.

Abstract

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.

• Authors: K Ito, R Miyamoto, H Tani, S Kurita, M Kobayashi, K Tamura, M Bonkobara
• Journal: Journal of veterinary pharmacology and therapeutics (J Vet Pharmacol Ther) Vol. 41 Issue 1 Pg. e45-e48 (Feb 2018) ISSN: 1365-2885 [Electronic] England
• PMID: 28833247 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Receptor, EphA2
• Dasatinib

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western (veterinary)
• Cell Line, Tumor
• Dasatinib (pharmacology)
• Disease Models, Animal
• Dog Diseases (drug therapy)
• Dogs
• Female
• Histiocytic Sarcoma (drug therapy, veterinary)
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Mitotic Index (veterinary)
• Neoplasm Transplantation (veterinary)
• Receptor, EphA2 (metabolism)