Literature DB >> 26711554

Suppression of colitis-associated carcinogenesis through modulation of IL-6/STAT3 pathway by balsalazide and VSL#3.

Eun-Ju Do1, Sung Wook Hwang2, Sang-Yeob Kim1,3, Yeon-Mi Ryu1, Eun A Cho1, Eun-Ju Chung2, Sunha Park1, Hyo Jeong Lee4, Jeong-Sik Byeon2, Byong Duk Ye2, Dong-Hoon Yang2, Sang Hyoung Park2, Suk-Kyun Yang2, Jin-Ho Kim2, Seung-Jae Myung1,2.   

Abstract

BACKGROUND AND AIM: Recent studies suggest that the anti-inflammatory agent balsalazide (BSZ) and probiotic agent VSL#3 have potential therapeutic benefits for the treatment of patients with inflammatory bowel disease. However, their effectiveness in preventing colitis-associated carcinogenesis (CAC) remains uncertain. The aim of the present study was to determine the chemopreventive effects of BSZ and VSL#3 in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model.
METHODS: C57B/L6J mice were randomly divided into four groups: CAC group, BSZ group, VSL#3 group, and BSZ + VSL#3 group. After 2 weeks, the AOM/DSS model was induced by AOM injection followed by two cycles of 2% DSS.
RESULTS: During first and second cycles of DSS, the number of F4/80-positive macrophages was significantly lower in the drug-treated groups compared with the CAC group (P < 0.05). At the endpoint, the total numbers of tumors in the drug-treated groups were significantly low compared with the CAC group (P < 0.05), and the drug-treated groups had significantly lower F4/80-positive macrophages in the tumor stroma (P < 0.01). The protein production of macrophage inflammatory protein 1 beta, monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-10 in the colon tissues decreased in concordance with the plasma concentrations of the cytokines (P < 0.05). The drug-treated groups revealed lower expression of p-STAT3 compared with the CAC group. In addition, BCL2 decreased, and BAX increased markedly in the BSZ + VSL#3 group.
CONCLUSIONS: These results revealed that BSZ and VSL#3 have chemopreventive effects against CAC through IL-6/STAT3 suppression. BSZ and VSL#3 could be suitable options for chemoprevention of colorectal cancer.
© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Entities:  

Keywords:  IL-6; STAT3; VSL#3; balsalazide; colitis-associated carcinogenesis

Mesh:

Substances:

Year:  2016        PMID: 26711554     DOI: 10.1111/jgh.13280

Source DB:  PubMed          Journal:  J Gastroenterol Hepatol        ISSN: 0815-9319            Impact factor:   4.029


  17 in total

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