selleck screening library 05 versus control group. Treatment with the combination of 1000��M concentrations of piroxicam and deracoxib resulted in an increase in the number of cells in the G0/G1 phase and a decrease in the number of cells in the S and G2/M phase indicating the cell cycle arrest at G0/G1 phase correlating with the induction of apoptosis (Table 2). At the highest dose combination of two drugs, the percentage of cells in the G0/G1 phase was increased from 63.8 to 89.95% when compared with control. Conversely, the percentage of cells in S phase decreased from 22.48% to 8.27%, and G2/M phase cells decreased from 13.72% to 1.78%. Table 2Effects of piroxicam and deracoxib combination on cell cycle phase distribution of CMT-U27 cells. Data are expressed as mean values �� standard error of means shown with *P < 0.
05 versus control group.4. Discussion In recent years, experimental, epidemiological, and clinical studies have identified COX inhibitors as promising compounds in anticancer therapy. There is an ample evidence of the involvement of COX-1 and COX-2 in carcinogenesis for many different types of malignant tumor, and results of numerous studies indicate that various NSAIDS exert antiproliferative and antineoplastic effects on several canine cancer cell lines [20, 21, 26]. These findings have raised the possibility that COX inhibitors might also act as tumor suppressors. Deracoxib, a selective COX-2 inhibitor, and piroxicam, a nonselective COX inhibitor, and also frequently used drugs in veterinary medicine were evaluated to determine the cytotoxic effects on canine mammary carcinoma cells.
In the present study, we investigated firstly the in vitro effects of piroxicam and deracoxib on canine mammary carcinoma cell line CMT-U27. As a result, both drugs suppressed proliferation of canine mammary tumor cells in a concentration-dependent manner. No significant difference in cell viability was seen after incubating GSK-3 cells with piroxicam (50�C500��M) and deracoxib (50�C100��M), but highly significant cell proliferation inhibition was seen after 72h incubation with 1000��M piroxicam and 250, 500, and 1000��M deracoxib. In a previous investigation, it was shown that piroxicam inhibited cellular proliferation of canine mammary carcinoma in vitro at concentrations above 1��g/mL and induced apoptosis in a dose-dependent manner, and the authors suggested that the significant inhibition of proliferation and induction of apoptosis could only occur when drug concentrations were in excess that can be achieved in vivo following maximum recommended dose rate of piroxicam [21].
Royals and colleagues [20] reported that piroxicam and deracoxib significantly decreased the cell proliferation of highly metastatic canine osteosarcoma cells at ��500��M and ��100��M concentrations, respectively.