title: 5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis.
abstract: BACKGROUND
  Cyclooxygenase-2 (COX-2) is a key enzyme that produces prostaglandin E2 (PGE2) and plays an important role in colorectal tumor growth. In addition, recent researches focused on 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades PGE2. Here we determined the effect of 5-aminosalicylic acid (5-ASA) on COX-2 and 15-PGDH expression and investigated its preventive effect for colorectal cancer (CRC).
  
  
  METHODS
  HT-29 cells were used in the in vitro experiments. c-Ha-ras transgenic mice were employed in order to explore the chemopreventive effects. Western blotting analysis was performed and the protein expression of COX-2 and 15-PGDH was quantified.
  
  
  RESULTS
  5-ASA significantly suppressed COX-2 expression and induced 15-PGDH expression in HT-29 cells. In the transgenic mice, oral 5-ASA intake reduced the incidence of colorectal tumor formation and the tumor size. Furthermore, we observed a down-regulation of COX-2 and an up-regulation of 15-PGDH in the tissue from colons of these mice.
  
  
  CONCLUSIONS
  5-ASA exerts a preventive effect against colorectal tumor development through mediation of COX-2 and 15-PGDH expression.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yajima
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Shimamura
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Higuchi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Funakoshi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Takaishi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D019804:Mesalamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D019804:Mesalamine; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2