Canine
osteosarcoma is an insidious disease with few effective treatment modalities; therefore, use of pharmacologic intervention to improve mortality or morbidity is constantly sought. The use of
cyclooxygenase enzyme inhibitors has been an area of interest with limited efficacy based on retrospective examination of
tumor expression and in vivo cell proliferation models. Recently, examination of dual
cyclooxygenase and
5-lipoxygenase inhibitors in human and canine oncology suggests that
5-lipoxygenase inhibitors may be an effective approach in vitro and during
tumor induction in rodent models. Therefore, the authors decided to examine
5-lipoxygenase expression in primary canine
osteosarcoma samples and have shown that approximately 65% of
osteosarcomas label positive for cytoplasmic
5-lipoxygenase. Further examination of a cell culture and xenograft model shows similar
5-lipoxygenase expression. Surprisingly, a canine
5-lipoxygenase inhibitor (
tepoxalin) significantly reduced cell proliferation at physiologic doses in vitro and diminished xenograft
tumor growth in nude mice, suggesting that further investigation is needed. Traditionally, 5-lipoxygense leads to production of
lipid mediators, such as
leukotriene B(4) and
5-oxo-eicosatetraenoic acid, which, when added back to the media of
tepoxalin-treated cells, did not recover cell proliferation. The lack of nuclear staining in primary and xenografted
tumors and the lack of response to eicoasanoids suggest that
lipid mediator production is not the primary means by which
tepoxalin acts to alter proliferation. Regardless of the mechanisms involved in retarding cell proliferation, future investigation is warranted.