Piroxicam Increases Colon Tumorigenesis and Promotes Apoptosis in Mlh1+/-/Apc1638N/+ Mice

Background: The present study examines the effect of piroxicam, a non-steroidal anti-inflammatory drug, on tumor development in Mlh1+/-/Apc1638N/+ mice, in a preclinical model of human colon cancer. Materials and Methods: Mice were fed AIN-76A diet alone or premixed with piroxicam (60 ppm) for 9 weeks. The number, location and volume of tumors, and apoptosis in the flat mucosa were determined in small and large intestine. Results: Piroxicam reduced the number of tumors per mouse by 80% in the small intestine (0.1 vs. 0.5, p<0.05). In contrast, piroxicam increased tumor incidence (82% vs. 10%, p<0.01), tumor multiplicity (1.2 vs. 0.1, p<0.01) and tumor volume (2.1 vs. 0.2 mm3, p<0.01) in the colon. Apoptosis increased in the epithelium of the small intestine. Conclusion: Consistent with the increased apoptosis, piroxicam reduced tumors in the small intestine. In the cecum, piroxicam increased tumorigenesis but apoptosis was not decreased, suggesting that other mechanisms besides apoptosis are involved in the differential organ-specific effect on tumorigenesis of piroxicam in this colon cancer model.