Chemoprevention for colorectal tumorigenesis associated with chronic colitis in mice via apoptosis.
The mechanism of the suppressive effect of nonsteroidal anti-inflammatory drugs in azoxymethan and dextran sulfate sodium-induced colonic aberrant crypt foci/tumors associated with chronic colitis in mice was studied. With administration of sulindac, a cyclooxygenase-1 and -2 inhibitor, the mean number of colonic aberrant crypt foci/tumors was significantly smaller than that of controls. There was no significant difference in prostaglandin E2 content in the colonic mucosa between the groups. Furthermore, nimesulid, a cyclooxygenase-2 selective inhibitor, also suppressed colonic aberrant crypt foci/tumors as well as sulindac. Administration of nimesulid caused apoptosis indices to be significantly higher along with cyclooxygenase-2 expression being significantly lower than in controls. Apoptosis indices of 400 ppm group of nimesulid were significantly higher than that of 200 ppm group. Nonsteroidal anti-inflammatory drugs distinctly suppress the occurrence of aberrant crypt foci/tumors in this murine colitis-associated neoplasia model. Induction of apoptosis is a more important factor for chemoprevention than this reduction of prostaglandin E2.
First Dept. of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan. sorii@iwate-med.ac.jp
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Orii
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Yamaguchi
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Anzai
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Saito
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Chiba
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Suzuki
D000818:Animals; D017209:Apoptosis; D001397:Azoxymethane; D002273:Carcinogens; D018890:Chemoprevention / Q000379:methods*; D002908:Chronic Disease; D003092:Colitis / Q000150:complications / Q000517:prevention & control*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013467:Sulindac / Q000008:administration & dosage / Q000627:therapeutic use*; D014881:Water Supply
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D013467:Sulindac; D001397:Azoxymethane