EVALUATION OF IN-VITRO CYTOTOXICITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS AGAINST CANINE TUMOR-CELLS

Piroxicam and other nonsteroidal anti-inflammatory drugs (NSAID) have antitumor activity against naturally acquired cancer in dogs and human beings, and against experimentally induced tumors in rodents. We are investigating potential mechanisms of NSAID antitumor activity. The di rect cytotoxicity of piroxicam, indomethacin, and aspirin against 4 ca nine tumor cell lines (transitional cell carcinoma, squamous cell carc inoma, melanoma, and soft tissue sarcoma) was determined in short-term growth rate assays and in clonogenic assays. Piroxicam was evaluated alone and in combination with the lipoxygenase inhibitor zileuton, and in combination with the chemotherapeutic agents cisplatin and carbopl atin. The 50% inhibitory concentrations (IC50) against melanoma cells in short-term growth rate assays were: 530 mu M piroxicam, 180 mu M in domethacin, and greater than 1 mM aspirin. These IC50 values were over 10 times greater than serum concentrations of these drugs that could safely be achieved in vivo. The IC50 of zileuton combined with piroxic am (280 mu M) was not different from the IC50 of zileuton alone (230 m u M; ANOVA P = 0.47) in melanoma cells. Similarly, addition of piroxic am did not alter the IC50 of either cisplatin (1.6 mu M) or carboplati n (6.1 mu M) These results suggest that NSAID, at serum concentrations achievable in vivo, do not have direct cytotoxicity against canine tu mor cells tested. It is unlikely that the in vivo antitumor activity o f NSAID is attributable to a direct cytotoxic effect.