Abstract:

Introduction:

Cyclooxygenase-2 (COX-2) inhibitors are being used increasingly in cancer therapy. Although the effects of COX-2 inhibitors have been evaluated extensively in carcinomas, less is known about their effects in sarcomas. Since the majority of dogs with appendicular osteosarcoma (OSA) are treated for pain with a non-steroidal anti-inflammatory drug (some COX-2 selective) prior to definitive treatment, it is important to determine the effects that commonly used NSAIDS have on tumor cell growth. Methods:

Established canine osteosarcoma (POS, HMPOS and COS31) and canine fibroblast cell lines were maintained in culture under standard conditions. Cells were incubated with either deracoxib (1 uM to 500 uM) or piroxicam (1 uM to 1000 uM). Cell viability was assessed at 72 hours by cell counts and the MTT assay. The DNA fragmentation analysis was utilized to assess for apoptosis induction. Results:

Deracoxib concentrations 100 uM and piroxicam concentrations 500 uM significantly reduced mean cell viability of all three OSA cell lines (lowest cell viability percentages 20% and 32%, respectively). Deracoxib concentrations 250 uM and piroxicam concentrations 500 uM also reduced viability of fibroblasts; however, the cell viability percent was reduced to only 54% and 68%, respectively, of the control value. Exposure of OSA cells to cytotoxic concentrations of deracoxib and piroxicam did not result in DNA fragmentation. Conclusions:

Deracoxib and piroxicam demonstrated a cytotoxic effect on canine osteosarcoma cells. There was no evidence of apoptosis induction at the concentrations evaluated. Further investigation will need to be performed to determine whether either drug exhibits anti-tumor effects in vivo.

Document Type: Research article

DOI: 10.1111/j.1476-5810.2005.064ah.x

Affiliations: 1: University of Florida, College of Veterinary Medicine, Gainesville, FL, 32610.