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The tyrosine kinase inhibitor sorafenib decreases cell number and induces apoptosis in a canine osteosarcoma cell line
Authors:B Wolfesberger  Z Tonar  W Gerner  G Heiduschka  JG Thalhammer
Institution:a Department for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria
b Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
c Department of Natural Science, University of Veterinary Medicine, Vienna, Austria
d Department of Histology and Embryology, Faculty of Medicine Pilsen, Charles University, Prague, Czech Republic
e Department of Mechanics, Faculty of Applied Sciences, University of West Bohemia, Czech Republic
f Department of Otolaryngology, Medical University of Vienna, Vienna, Austria
Abstract:Canine osteosarcoma, an aggressive cancer with early distant metastasis, shows still despite good chemotherapy protocols poor long term survival. The aim of our study was to determine whether sorafenib, a novel multikinase inhibitor, has any effect on D-17 canine osteosarcoma cells.A cell proliferation kit was used for detecting surviving cells after treatment for 72 h with sorafenib or carboplatin or their combination. A significant decrease of neoplastic cells was observed after incubation with 0.5-16 μM sorafenib or with 80-640 μM carboplatin. Using immunocytochemistry for activated caspase 3 to evaluate apoptosis, we found significantly more positive cells in the sorafenib treated groups. Paradoxically, expression of the nuclear proliferation marker Ki-67 was also significantly higher in sorafenib treated cells. The drug sorafenib showed potent antitumour activity against D-17 canine osteosarcoma cells in vitro, suggesting a potential as a therapeutic tool in the treatment of bone cancer in dogs.
Keywords:Sorafenib  Apoptosis  Canine osteosarcoma  Carboplatin
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