The tyrosine kinase inhibitor sorafenib decreases cell number and induces apoptosis in a canine osteosarcoma cell line.
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 microM sorafenib or with 80-640 microM 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.
Wolfesberger
B
B
Department for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria. birgitt.wolfesberger@vu-wien.ac.at
Tonar
Z
Z
Gerner
W
W
Skalicky
M
M
Heiduschka
G
G
Egerbacher
M
M
Thalhammer
J G
JG
Walter
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000188:drug therapy* / Q000201:enzymology; D004285:Dogs; D005434:Flow Cytometry; D019394:Ki-67 Antigen / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009536:Niacinamide / Q000031:analogs & derivatives; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D010671:Phenylurea Compounds; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D019394:Ki-67 Antigen; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D053148:Caspase 3