title: Suppression of colitis-associated carcinogenesis through modulation of IL-6/STAT3 pathway by balsalazide and VSL#3.
abstract: OBJECTIVE
  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.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Do
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Hwang
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.|Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
authors.forename: Yeon-Mi
authors.initials: YM
authors.lastname: Ryu
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
authors.forename: Eun A
authors.initials: EA
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chung
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
authors.forename: Sunha
authors.initials: S
authors.lastname: Park
authors.affiliation: Health Screening & Promotion Center, Asan Medical Center, Seoul, Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Jeong-Sik
authors.initials: JS
authors.lastname: Byeon
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Byong Duk
authors.initials: BD
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Sang Hyoung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.|Department of Gastroenterology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Myung
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D010659:Phenylhydrazines / Q000494:pharmacology*; D010766:Phosphorylation; D019936:Probiotics / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; C494827:Bax protein, mouse; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D010659:Phenylhydrazines; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051028:bcl-2-Associated X Protein; C577686:interleukin-6, mouse; C052617:Bcl2 protein, mouse; D019804:Mesalamine; D016264:Dextran Sulfate; D001397:Azoxymethane; C038637:balsalazide
keywords: IL-6; STAT3; VSL#3; balsalazide; colitis-associated carcinogenesis