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Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands
BACKGROUND: It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS)...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1156872/ https://www.ncbi.nlm.nih.gov/pubmed/15892897 http://dx.doi.org/10.1186/1471-2407-5-46 |
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author | Kohno, Hiroyuki Suzuki, Rikako Sugie, Shigeyuki Tanaka, Takuji |
author_facet | Kohno, Hiroyuki Suzuki, Rikako Sugie, Shigeyuki Tanaka, Takuji |
author_sort | Kohno, Hiroyuki |
collection | PubMed |
description | BACKGROUND: It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a PPARγ ligand) and bezafibrate (a PPARα ligand) inhibit colitis-related colon carcinogenesis using our model to evaluate the efficacy of these drugs in prevention of IBD-related colon carcinogenesis. METHODS: Female CD-1 (ICR) mice were given a single intraperitoneal administration of AOM (10 mg/kg body weight) and followed by one-week oral exposure of 2% (w/v) DSS in drinking water, and then maintained on the basal diets mixed with or without nimesulide (0.04%, w/w), troglitazone (0.05%, w/w), and bezafibrate (0.05%, w/w) for 14 weeks. The inhibitory effects of dietary administration of these compounds were determined by histopathological and immunohistochemical analyses. RESULTS: Feeding with nimesulide and troglitazone significantly inhibited both the incidence and multiplicity of colonic adenocarcinoma induced by AOM/DSS in mice. Bezafibrate feeding significantly reduced the incidence of colonic adenocarcinoma, but did not significantly lower the multiplicity. Feeding with nimesulide and troglitazone decreased the proliferating cell nuclear antigen (PCNA)-labeling index and expression of β-catenin, COX-2, inducible nitric oxide synthase (iNOS) and nitrotyrosine. The treatments increased the apoptosis index in the colonic adenocarcinoma. Feeding with bezafibrate also affected these parameters except for β-catenin expression in the colonic malignancy. CONCLUSION: Dietary administration of nimesulide, troglitazone and bezafibrate effectively suppressed the development of colonic epithelial malignancy induced by AOM/DSS in female ICR mice. The results suggest that COX-2 inhibitor and PPAR ligands could serve as an effective agent against colitis-related colon cancer development. |
format | Text |
id | pubmed-1156872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-11568722005-06-22 Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands Kohno, Hiroyuki Suzuki, Rikako Sugie, Shigeyuki Tanaka, Takuji BMC Cancer Research Article BACKGROUND: It is generally assumed that inflammatory bowel disease (IBD)-related carcinogenesis occurs as a result of chronic inflammation. We previously developed a novel colitis-related mouse colon carcinogenesis model initiated with azoxymethane (AOM) and followed by dextran sodium sulfate (DSS). In the present study we investigated whether a cyclooxygenase (COX)-2 inhibitor nimesulide and ligands for peroxisome proliferator-activated receptors (PPARs), troglitazone (a PPARγ ligand) and bezafibrate (a PPARα ligand) inhibit colitis-related colon carcinogenesis using our model to evaluate the efficacy of these drugs in prevention of IBD-related colon carcinogenesis. METHODS: Female CD-1 (ICR) mice were given a single intraperitoneal administration of AOM (10 mg/kg body weight) and followed by one-week oral exposure of 2% (w/v) DSS in drinking water, and then maintained on the basal diets mixed with or without nimesulide (0.04%, w/w), troglitazone (0.05%, w/w), and bezafibrate (0.05%, w/w) for 14 weeks. The inhibitory effects of dietary administration of these compounds were determined by histopathological and immunohistochemical analyses. RESULTS: Feeding with nimesulide and troglitazone significantly inhibited both the incidence and multiplicity of colonic adenocarcinoma induced by AOM/DSS in mice. Bezafibrate feeding significantly reduced the incidence of colonic adenocarcinoma, but did not significantly lower the multiplicity. Feeding with nimesulide and troglitazone decreased the proliferating cell nuclear antigen (PCNA)-labeling index and expression of β-catenin, COX-2, inducible nitric oxide synthase (iNOS) and nitrotyrosine. The treatments increased the apoptosis index in the colonic adenocarcinoma. Feeding with bezafibrate also affected these parameters except for β-catenin expression in the colonic malignancy. CONCLUSION: Dietary administration of nimesulide, troglitazone and bezafibrate effectively suppressed the development of colonic epithelial malignancy induced by AOM/DSS in female ICR mice. The results suggest that COX-2 inhibitor and PPAR ligands could serve as an effective agent against colitis-related colon cancer development. BioMed Central 2005-05-16 /pmc/articles/PMC1156872/ /pubmed/15892897 http://dx.doi.org/10.1186/1471-2407-5-46 Text en Copyright © 2005 Kohno et al; licensee BioMed Central Ltd. |
spellingShingle | Research Article Kohno, Hiroyuki Suzuki, Rikako Sugie, Shigeyuki Tanaka, Takuji Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands |
title | Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands |
title_full | Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands |
title_fullStr | Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands |
title_full_unstemmed | Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands |
title_short | Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands |
title_sort | suppression of colitis-related mouse colon carcinogenesis by a cox-2 inhibitor and ppar ligands |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1156872/ https://www.ncbi.nlm.nih.gov/pubmed/15892897 http://dx.doi.org/10.1186/1471-2407-5-46 |
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