Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam.
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.
Jacoby
R F
RF
Department of Medicine/Division of Gastroenterology, University of Wisconsin, Madison, Wisconsin 53792, USA.
Marshall
D J
DJ
Newton
M A
MA
Novakovic
K
K
Tutsch
K
K
Cole
C E
CE
Lubet
R A
RA
Kelloff
G J
GJ
Verma
A
A
Moser
A R
AR
Dove
W F
WF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000097:blood / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D003433:Crosses, Genetic; D004305:Dose-Response Relationship, Drug; D005260:Female; D017491:Genes, APC; D006579:Heterozygote; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010894:Piroxicam / Q000097:blood / Q000494:pharmacology*; D011897:Random Allocation; D013929:Thromboxane B2 / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D010894:Piroxicam; D013929:Thromboxane B2