Related Experiment Video
Updated: Sep 26, 2026
Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine
Published on: October 13, 2023
Chemoprevention for colorectal tumorigenesis associated with chronic colitis in mice via apoptosis
1First Dept. of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Iwate, Japan. sorii@iwate-med.ac.jp
Abstract:
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.
Insights
Nonsteroidal anti-inflammatory drugs suppress colon tumors in mice with colitis. This chemoprevention is linked to increased apoptosis, not reduced prostaglandin E2 levels.
Area of Science:
- Gastroenterology
- Oncology
- Pharmacology
Background:
- Chronic colitis can lead to colonic aberrant crypt foci and tumors.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to have chemopreventive effects.
Purpose of the Study:
- To investigate the mechanism by which NSAIDs suppress colonic aberrant crypt foci/tumors in a murine model of colitis-associated neoplasia.
- To determine whether prostaglandin E2 reduction or apoptosis induction is the primary mechanism of NSAID chemoprevention.
Main Methods:
- Azoxymethane and dextran sulfate sodium were used to induce colitis and neoplasia in mice.
- Mice were treated with sulindac (a COX-1 and COX-2 inhibitor) or nimesulide (a COX-2 selective inhibitor).
- Colonic aberrant crypt foci/tumors, prostaglandin E2 levels, apoptosis indices, and cyclooxygenase-2 expression were analyzed.
Main Results:
- Both sulindac and nimesulide significantly suppressed the formation of colonic aberrant crypt foci/tumors.
- No significant difference in prostaglandin E2 levels was observed between NSAID-treated groups and controls.
- Nimesulide treatment significantly increased apoptosis indices and decreased cyclooxygenase-2 expression, with higher doses showing greater effects on apoptosis.
Conclusions:
- NSAIDs effectively suppress colitis-associated colonic neoplasia in mice.
- The chemopreventive mechanism of NSAIDs in this model is primarily mediated by the induction of apoptosis.
- Apoptosis induction is a more critical factor in NSAID-mediated chemoprevention than the reduction of prostaglandin E2.
