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The selective cyclooxygenase-2 inhibitor mavacoxib (Trocoxil) exerts anti-tumour effects in vitro independent of cyclooxygenase-2 expression levels

Vet Comp Oncol. 2019 Jun;17(2):194-207. doi: 10.1111/vco.12470. Epub 2019 Mar 13.

Abstract

The inducible inflammatory enzyme cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2 ) are prominent tumour promoters, and expression of COX-2 is elevated in a number of tumours of both humans and canines. Targeting COX-2 in cancer is an attractive option because of readily available non-steroidal anti-inflammatory drugs (NSAIDs), and there is a clear epidemiological link between NSAID use and cancer risk. In this study, we aim to establish the anti-tumourigenic effects of the selective, long-acting COX-2 inhibitor mavacoxib. We show here that mavacoxib is cytotoxic to a panel of human and canine osteosarcoma, mammary and bladder carcinoma cancer cell lines; that it can induce apoptosis and inhibit the migration of these cells. Interestingly, we establish that mavacoxib can exert these effects independently of elevated COX-2 expression. This study highlights the potential novel use of mavacoxib as a cancer therapeutic, suggesting that mavacoxib may be an effective anti-cancer agent independent of tumour COX-2 expression.

Keywords: COX-2; COX-2 independent effects; canine; comparative oncology; mavacoxib.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / veterinary
  • Cell Line, Tumor / drug effects*
  • Cyclooxygenase 2 Inhibitors / metabolism*
  • Dog Diseases / drug therapy
  • Dogs
  • Female
  • Humans
  • Osteosarcoma / drug therapy
  • Osteosarcoma / veterinary
  • Pyrazoles / pharmacology*
  • Pyroptosis
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / veterinary

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • 4-(5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide

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