Celecoxib and rofecoxib potentiate chronic colitis and premalignant changes in interleukin 10 knockout mice.
Nonsteroidal anti-inflammatory drugs decrease sporadic colorectal carcinoma and adenomas in patients with familial adenomatous polyposis and in rodent models of sporadic colon cancer and familial adenomatous polyposis. Similarly, selective cyclooxygenase 2 inhibitors decrease adenomas in humans and rodents. However, their effects on chronic colitis and colitis-associated neoplasia are unknown. Interleukin 10-/- mice (C57/B6) were fed regular chow (n = 20) or chow with celecoxib (1,500 ppm, n = 18) or rofecoxib (75 ppm, n = 20) for 12 weeks. Twenty-eight percent of the celecoxib group died versus 5% of the control and rofecoxib groups (p < 0.05 compared with control). Celecoxib and rofecoxib increased the incidence of colitis (26% vs. 92% and 68%, p < 0.01), colitis score (0.4 +/- 0.2 vs. 2.5 +/- 0.3 and 2 +/- 0.4, p < 0.01), aberrant crypt foci (0.5 +/- 0.3 vs. 3.7 +/- 2.6 and 2.8 +/- 0.7, p < 0.01), aberrant crypts per mouse (4.11 +/- 2.1 vs. 41.2 +/- 9.7 and 27.1 +/- 7.5, p < 0.01) and dysplasia (11% vs. 54% and 42%, p < 0.01). Similarly, indomethacin (9 ppm, n = 15) increased colitis score, aberrant crypt foci, and dysplasia after 27 days of treatment. Two selective cyclooxygenase 2 inhibitors exacerbate colitis and premalignant changes in the interleukin 10-/- mouse model of chronic colitis and colitis-associated colon carcinoma.
Hegazi
Refaat A F
RA
Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center and Pittsburgh Veterans Administration Medical Center, Pittsburgh, Pennsylvania 15213, U.S.A.
Mady
Hussam H
HH
Melhem
Mona F
MF
Sepulveda
Antonia R
AR
Mohi
Mohamed
M
Kandil
Hossam M
HM
D000818:Animals; D000068579:Celecoxib; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology*; D007783:Lactones / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D011720:Pyrazoles; D013449:Sulfonamides / Q000633:toxicity*; D013450:Sulfones
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D016753:Interleukin-10; D000068579:Celecoxib