Honors College Thesis
 

The Effect of Non-Steroidal Anti-Inflammatory Drugs on Canine Transitional Cell Carcinoma and Its Correlation with Cyclooxygenase-2 Expression

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  • Canine transitional cell carcinoma (TCC) has been shown to have a substantial inflammatory component. It exhibits genotypic and morphologic elements that resemble its human counterpart. Cyclooxygenases (COX) are key enzymes in the synthesis of proinflammatory molecules, such as prostaglandins. Excess prostaglandin production through cyclooxygenases may promote oncogenesis and progression of certain cancers. Inhibition of COX-2 represents a therapeutic target for clinicians treating several cancers, including canine TCC. With most traditional NSAIDs, gastrointestinal side effects are concerning. Firocoxib, a novel second-generation NSAID, exhibits 350-430 fold selectivity for COX-2 and is approved for veterinary use, including treatment of canine TCC. To understand the effects of Firocoxib in vitro, we evaluated the cyclooxygenase profile for 5 TCC cell lines, as well as primary tissue samples from patients diagnosed with TCC. All cell lines expressed ptgs-2; TCC tissue samples varied in their ptgs-2 expression. Changes in prostaglandin E₂ (PGE₂) concentration, angiogenic factors, oxidative stress, ptgs-2 expression, and the proteome after Firocoxib treatment were investigated. Two TCC cell lines were treated with Firocoxib in cell proliferation assays to investigate metabolic effects of COX-2 inhibition. Significant decreases in PGE₂ concentrations after Firocoxib treatment were noticed, despite high basal PGE₂ production. Unique proteomic changes were discovered.
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