Abstract | PURPOSE: METHODS: RESULTS: In a colitis-associated cancer model, treatment with the IKKbeta inhibitors NBD peptide and IMD-0354 significantly reduced the number of tumors compared with the untreated group. The tumors were also significantly smaller in the inhibitor-treated mice than in the untreated mice. Macrophage and neutrophil infiltration decreased with the inhibitor treatment. NF-kappaB activation and the expression of Cox-2 and iNOS were observed in tumor tissues, and the inhibitors ameliorated their expression. These inhibitors blocked NF-kappaB activation and the expression of proinflammatory cytokines mediated by the culture supernatant of inflamed colon in murine primary macrophages. In-vitro and in-vivo experiments showed that these drugs, especially NBD peptide, could also inhibit the proliferation of colonic epithelial cells. CONCLUSION: These results imply that IKKbeta-targeted NF-kappaB blockade is an attractive therapeutic approach for the prevention of colitis-associated tumors.
|
Authors | Yoku Hayakawa, Shin Maeda, Hayato Nakagawa, Yohko Hikiba, Wataru Shibata, Kei Sakamoto, Ayako Yanai, Yoshihiro Hirata, Keiji Ogura, Susumu Muto, Akiko Itai, Masao Omata |
Journal | Journal of gastroenterology
(J Gastroenterol)
Vol. 44
Issue 9
Pg. 935-43
( 2009)
ISSN: 1435-5922 [Electronic] Japan |
PMID | 19557302
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents
- Benzamides
- NBD peptide, mouse
- NF-kappa B
- Peptides
- N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide
- Dextran Sulfate
- I-kappa B Kinase
- Azoxymethane
|
Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Azoxymethane
(toxicity)
- Benzamides
(pharmacology)
- Cell Proliferation
(drug effects)
- Colitis
(complications, pathology)
- Colorectal Neoplasms
(drug therapy, etiology, physiopathology)
- Dextran Sulfate
(toxicity)
- Drug Delivery Systems
- Drug Screening Assays, Antitumor
- I-kappa B Kinase
(antagonists & inhibitors)
- Macrophages
(drug effects, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- NF-kappa B
(antagonists & inhibitors)
- Neutrophil Infiltration
(drug effects)
- Peptides
(pharmacology)
|