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).
MATERIALS AND 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.
CONCLUSION
5-ASA exerts a preventive effect against colorectal tumor development through mediation of COX-2 and 15-PGDH expression.

Links

Publisher Full Text

Authors

Miyoshi J, Yajima T, Shimamura K, Matsuoka K, Okamoto S, Higuchi H, Funakoshi S, Takaishi H, Hibi T

Institution

Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

Source

Anticancer research 32:4 2012 Apr pg 1193-202

MeSH

Animals
Colorectal Neoplasms
Cyclooxygenase 2
HT29 Cells
Humans
Hydroxyprostaglandin Dehydrogenases
Mesalamine
Mice
Mice, Inbred C57BL
Mice, Transgenic

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22493349