The Investigation of the Effectiveness of COX-1 and COX-2 Inhibitors in Canine Mammary Tumour Cell Line
F. Ustun Alkan1; O. Ustuner1; T. Bakirel1; S. Cinar2; G. Erten2; G. Deniz2
Mammary tumours are the most common neoplasms of the female dogs. There is a critical need for the discovery and development of novel therapy approaches for cancer therapy. In recent years, several studies have shown nonsteroidal antiinflammatory drugs are effective in the prevention and treatment of various types of cancer.
The present study was designed to determine the antineoplastic mechanism of COX-1 and COX-2 inhibitors and to evaluate the therapeutic efficiency of the combination of these drugs in CMT-U27 canine mammary carcinoma cell line.
CMT-U27 cells were treated with piroxicam (COX-1 inhibitor) and deracoxib (COX-2 inhibitor) at 50–1000 µM concentrations as both single and combined treatments for 72 h. Cell viability was measured using the MTT assay. Apoptosis detection and cell cycle analyses were performed by flow cytometry.
Reductions in cell growth were observed at high concentrations of piroxicam and deracoxib in both single and combined treatments. Flow cytometric analyses revealed that high concentrations of piroxicam and deracoxib induced cell death via an apoptotic process. Concomitant treatment resulted in significant induction of apoptosis at lower concentrations. Also, deregulation of the cell cycle was observed which correlated with the observed effects of COX inhibitors in CMT-U27 cells.
These data suggest that combination therapy consisting of piroxicam and deracoxib may be an attractive approach for the treatment of canine mammary carcinoma. Further, in vivo clinical studies should be considered before they could be used alone or in combinations with other agents for cancer chemoprevention.