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BMC Cancer

, 5:46

First Online: 16 May 2005Received: 15 January 2005Accepted: 16 May 2005DOI: 10.1186-1471-2407-5-46

Cite this article as: Kohno, H., Suzuki, R., Sugie, S. et al. BMC Cancer 2005 5: 46. doi:10.1186-1471-2407-5-46

Abstract

BackgroundIt 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.

MethodsFemale 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.

ResultsFeeding 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.

ConclusionDietary 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.

AbbreviationsAOMazoxymethane

ACFaberrant crypt foci

CRCColorectal cancer

COX-2cyclooxygenase-2

DSSdextran sodium sulfate

FAPfamilial adenomatous polyposis

HandEhematoxylin and eosin

IBDinflammatory bowel disease

iNOSinducible nitric oxide synthase

NSAIDnon-steroidal anti-inflammatory drug

PPARperoxisome proliferator-activated receptor

PCNAproliferating cell nuclear antigen

ssDNAsingle stranded DNA

UCulcerative colitis.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-5-46 contains supplementary material, which is available to authorized users.





Autor: Hiroyuki Kohno - Rikako Suzuki - Shigeyuki Sugie - Takuji Tanaka

Fuente: https://link.springer.com/







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