期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 22, 期 44, 页码 9727-9733出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v22.i44.9727
关键词
Inflammatory bowel disease; Ulcerative colitis; Colorectal cancer; Infliximab; AOM-DSS model; Cancer on chronic colitis
资金
- Crohn's and Colitis Foundation of America, Research Fellowship Award [CON125252]
- European Crohn's and Colitis Organization Grant
- Societa Italiana di Gastroenterologia prize
AIM To explore the influence of Infliximab (IFX) on cancer progression in a murine model of colonic cancer associated to chronic colitis. METHODS AOM/DSS model was induced in C57BL/6 mice. Mice were injected with IFX (5 mg/kg) during each DSS cycle while control mice received saline. Body weight, occult blood test and stool consistency were measured to calculate the disease activity index (DAI). Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential IFX role on metabolic activity and proliferation. Cells were incubated with TNF-alpha or IFX or TNF-alpha plus IFX, and cell vitality was evaluated after 6, 24 and 48 h. The same setting was used after pre-incubation with TNF-alpha for 24 h. RESULTS IFX significantly reduced DAI and body weight loss in mice compared with controls, preserving also colon length at sacrifice. Histological score was also reduced in treated mice. At macroscopic analysis, IFX treated mice showed a lower number of tumor lesions compared to controls. This was confirmed at microscopic analysis, although differences were not statistically significant. In vitro, IFX treated CT26 maintained similar proliferation ability at MTT test, both when exposed to IFX alone and when associated to TNF-alpha. CONCLUSION IFX did not increase colonic cancer risk in AOM-DSS model of cancer on chronic colitis nor influence directly the proliferation of murine colon cancer epithelial cells.
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