Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses
Article first published online: 12 APR 2011
© 2011 Blackwell Publishing Ltd
Journal of Veterinary Pharmacology and Therapeutics
Volume 35, Issue 1, pages 97–104, February 2012
How to Cite
TAKEUCHI, Y., FUJINO, Y., FUKUSHIMA, K., WATANABE, M., NAKAGAWA, T., OHNO, K., SASAKI, N., SUGANO, S. and TSUJIMOTO, H. (2012), Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses. Journal of Veterinary Pharmacology and Therapeutics, 35: 97–104. doi: 10.1111/j.1365-2885.2011.01296.x
- Issue published online: 6 JAN 2012
- Article first published online: 12 APR 2011
- (Paper received 17 November 2010; accepted for publication 24 February 2011)
Takeuchi, Y., Fujino, Y., Fukushima, K., Watanabe, M., Nakagawa, T., Ohno, K., Sasaki, N., Sugano, S., Tsujimoto, H. Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses. J. vet. Pharmacol. Therap. 35, 97–104.
Tyrosine kinase inhibitors (TKIs) can be important in the treatment of canine mast cell tumor (cMCT). Meanwhile, some TKIs have been identified as substrates for ABCB1. The inhibitory effect of four TKIs (axitinib, imatinib, masitinib, and vatalanib) for proliferation and phosphorylation of c-Kit receptor as well as the expression and function of ABCB1 were investigated in three cMCT cell lines (HRMC, VIMC1, and CMMC1). The IC50 values of the TKIs in HRMC, the only cell line with wild-type KIT, were clearly higher than those in CMMC1 and VIMC1. In HRMC and CMMC1, both the growth and phosphorylation of c-Kit receptor were suppressed proportionally by the TKIs. VIMC1 required higher concentrations for the inhibition of c-Kit receptor phosphorylation than those in cell growth. The treatment with cyclosporine increased the effects of the TKIs on VIMC1 since ABCB1 was expressed in VIMC1. The results indicated that cMCT cell lines harboring wild-type KIT had lower sensitivity to TKIs. The growth of VIMC1 was seemingly reduced by TKIs through the inhibition of other tyrosine kinases than c-Kit receptor. There was little influence of ABCB1 on TKI effects to the proliferation of VIMC1. These results will be helpful to understand the different sensitivity to TKIs in cMCT patients.