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Chemoprevention of Spontaneous Intestinal Adenomas in the Apc ^Min Mouse Model by the Nonsteroidal Anti-inflammatory Drug Piroxicam¹

Departments of Medicine/Division of Gastroenterology [R. F. J., D. J. M., K. N.] and Human Oncology [R. F. J., A. V., A. R. M.], and the Comprehensive Cancer Center [R. F. J., M. A. N., K. T., C. E. C., A. V., A. R. M.], University of Wisconsin, Madison, Wisconsin 53792; William S. Middleton Memorial Veteran's Hospital, Madison, Wisconsin 53705 [R. F. J., D. J. M., C. E. C.]; Department of Biostatistics, University of Wisconsin, Madison, Wisconsin 53792 [M. A. N.]; Chemoprevention Branch, National Cancer Institute-DCPC, Bethesda, Maryland 20892 [R. A. L., G. J. K.]; and McArdle Laboratory for Cancer Research, Madison, Wisconsin 53706 [A. R. M., W. F. D.]

C57BL/6J-Min/+ mice (n = 56), heterozygous for a nonsense mutation in the Apc gene, were randomized at weaning to seven groups, including groups treated with piroxicam at 0, 50, 100, and 200 ppm in the AIN93G diet. After only 6 weeks of treatment, intestinal adenomas and aberrant crypt foci were counted, and serum levels of piroxicam and thromboxane B₂ were quantitated. Tumor multiplicity was decreased in a dose-dependent 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 B₂ levels in plasma also decreased monotonically in parallel to the decrease in tumor multiplicity, consistent with the prostaglandin inhibitory effect of piroxicam. The Min mouse model demonstrates that the nonsteroidal anti-inflammatory drug piroxicam has strong biological and therapeutic effects, potentially useful for prevention of the early adenoma stage of tumor development.

¹ This study was funded in part by NIH Grants CA14520, CA59352, CA50585, and CA64677; NIH Contract NCI/CN45591-72; and a Merit Review grant from the Department of Veteran's Affairs.

² To whom requests for reprints should be addressed, at H6/516 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792. Phone: (608) 262-7056; Fax: (608) 262-7641; E-mail: jacoby@facstaff.wisc.edu.

Received 11/20/95. Accepted 1/ 2/96.

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