title: Induction of VEGF by tepoxalin does not lead to increased tumour growth in a canine osteosarcoma xenograft.
abstract: The purpose of this study was to determine the impact of the non-steroidal anti-inflammatory drug tepoxalin on canine tumour cell growth and describe the changes associated with tepoxalin treatment. In vitro experiments were performed to assess tepoxalin-associated alterations in tumour cell growth. Clinically achievable tepoxalin concentrations did not significantly alter tumour cell growth in vitro. Vascular endothelial growth factor (VEGF) production and hypoxia-inducible factor-1α dose-dependently increased in vitro in the presence of tepoxalin. A canine osteosarcoma xenograft was used to determine in vivo effects of tepoxalin on tumour growth and angiogenesis. Despite increased VEGF in vitro, there was a significant growth delay associated with tepoxalin treatment. Normal dogs were administered tepoxalin to assess effects on systemic VEGF production, but not found to have significantly increased VEGF. These data suggest that tepoxalin may moderately inhibit tumour growth and may be administered as an analgesic to tumour-bearing dogs.
authors.affiliation: Department of Clinical Sciences, Animal Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Sottnik
authors.forename: R J
authors.initials: RJ
authors.lastname: Hansen
authors.forename: D L
authors.initials: DL
authors.lastname: Gustafson
authors.forename: S W
authors.initials: SW
authors.lastname: Dow
authors.forename: D H
authors.initials: DH
authors.lastname: Thamm
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D049109:Cell Proliferation / Q000187:drug effects*; D004283:Dog Diseases / Q000188:drug therapy / Q000473:pathology*; D004285:Dogs; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011720:Pyrazoles; D042442:Vascular Endothelial Growth Factors; C073135:tepoxalin