The University of Georgia College of Veterinary Medicine

Georgia Veterinary Scholars Program

GVSP Summer 2011 Scholars

Georgia Veterinary Scholar	Faculty Mentor

Amanda Vance University of Georgia Class of 2014	Dr. Jessica Lawrence Department of Small Animal Medicine UGA College of Veterinary Medicine

Investigation of the use of masitinib and radiation on feline injection site sarcoma cells

Amanda Vance and Jessica Lawrence and Michelle Turek and Robert Gogal, Jr. and Michel Vandenplas

Injection site sarcoma (ISS) is a soft tissue tumor that can develop in cats where inactivated vaccines are administered. Despite aggressive therapy with radiation, surgery and/or chemotherapeutics, ISS has traditionally been almost uniformly fatal, thus warranting new treatment modalities. Platelet derived growth factor receptor (PDGFR) is a protein kinase critical in ISS cell survival and signal transduction. Masitinib (AB Science, Paris, France), a commercially available veterinary tyrosine kinase inhibitor, is highly selective for the PDGFR signaling pathway and has been shown to reduce PDGFR signaling in a dose-dependent fashion in many species. Recently, masitinib was shown to reduce cell growth and to promote apoptosis of feline tumor cells in culture. As radiation is a conventional therapy used in clinical management of feline ISS, the combined in vitro effects of masitinib and radiation in 2 ISS cell lines were investigated. The objective of this study was to determine if the radiosensitivity of ISS cells was altered in the presence of masitinib. Alamar Blue proliferation assays were used to generate dose-response curves following treatment with varying doses of masitinib (0-86 µM) and radiation (0-6 Gy). DNA double strand break induction, the principal target of radiation therapy, was measured using a commercially available ELISA assay. At lower doses of masitinib, radiation induced significant growth inhibition, however this inhibitory effect was abolished at higher doses. The commercial ELISA proved simple to use and showed a significant increase in double strand break induction in irradiated cells compared to control cells. Further in vitro investigation into the role of masitinib on altering ISS cell responses to radiation are warranted given these preliminary findings.