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The radiosensitizing effect of the aurora kinase inhibitors,ENMD‐2076, on canine mast cell tumours in vitro
Authors:K Shiomitsu  E Sajo  C Rubin  I Sehgal
Institution:1. Department of Veterinary Clinical Sciences, Cancer Treatment Unit, Louisiana State University, Baton Rouge, LA, USA;2. Department of Physics, Medical Physics Program, University of Massachusetts Lowell, Lowell, MA, USA;3. Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA, USA
Abstract:ENMD‐2076 is an aurora kinase inhibitor that also has multi‐target tyrosine kinase inhibitor properties. In this study, the mRNA and the protein expression of aurora‐A and aurora‐B were evaluated in three canine mast cell tumour cell lines. Dose‐dependent cytotoxicity was seen in the cells treated, and it affected the cell cycle with cells in the G2/M phase being selectively killed. The cells were also evaluated for radiosensitivity with/without ENMD‐2076, and radiosensitization was seen after 3 Gy and 6 Gy exposures with ENMD‐2076 for 48 h. Protein expression of caspase‐3 was gradually increased, and the expression intensity was highest at 24 h post irradiation in cells without ENMD‐2076 treatment, which indicates that radiation exposure with ENMD‐2076‐induced cell death faster than radiation treatment alone. Our study results suggest the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy.
Keywords:aurora kinase inhibitors  canine mast cell tumours  ENMD‐2076  radiosensitivity
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