CHEMOPREVENTION OF SPONTANEOUS INTESTINAL ADENOMAS IN THE APC (MIN) MOUSE MODEL BY THE NONSTEROIDAL ANTIINFLAMMATORY DRUG PIROXICAM

C57BL/6J-Min/+ mice (n = 56), heterozygous for a nonsense mutation in the Apc gene, sere randomized at weaning to seven groups, including gr oups treated with piroxicam at 0, 50, 100, and 200 ppm in the AIN93G d iet. After only 6 weeks of treatment, intestinal adenomas and aberrant crypt foci were counted, and serum levels of piroxicam and thromboxan e B-2 were quantitated. Tumor multiplicity was decreased in a dose-dep endent manner from 17.3 +/- 2.7 in the control to 2.1 +/- 1.1 (12%) in the high-dose piroxicam group (P < 0.001). Thromboxane B-2 levels in plasma also decreased monotonically in parallel to the decrease in tum or multiplicity, consistent with the prostaglandin inhibitory effect o f piroxicam. The Min mouse model demonstrates that the nonsteroidal an ti-inflammatory drug piroxicam has strong biological and therapeutic e ffects, potentially useful for prevention of the early adenoma stage o f tumor development.