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Suppression of colitis‐associated carcinogenesis through modulation of IL‐6/STAT3 pathway by balsalazide and VSL#3
Author(s) -
Do Eunju,
Hwang Sung Wook,
Kim SangYeob,
Ryu YeonMi,
Cho Eun A.,
Chung EunJu,
Park Sunha,
Lee Hyo Jeong,
Byeon JeongSik,
Ye Byong Duk,
Yang DongHoon,
Park Sang Hyoung,
Yang SukKyun,
Kim JinHo,
Myung SeungJae
Publication year - 2016
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13280
Subject(s) - azoxymethane , medicine , colitis , gastroenterology , inflammatory bowel disease , colorectal cancer , immunology , interleukin , cytokine , pharmacology , cancer , disease
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.