COX inhibitor, suppression of polyposis, and chemoprevention.

  • OSHIMA Masanobu
    Department of Pharmacology, Kyoto University Graduate School of Medicine
  • TAKETO Makoto
    Department of Pharmacology, Kyoto University Graduate School of Medicine

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Other Title
  • ノックアウトマウスの創薬への応用  COX‐2阻害薬,腸ポリープ症抑制,そして癌の化学予防
  • COX-2阻害薬,腸ポリープ症抑制,そして癌の化学予防
  • COX 2 ソガイヤク チョウ ポリープショウ ヨクセイ ソシテ ガン ノ カガク ヨボウ

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Abstract

Early experiments using carcinogen-induced rat intestinal tumor models demonstrated the inhibitory effects of non-steroidal anti-inflammatory drugs (NSAIDs) on intestinal tumorigenesis. Furthermore, epidemiological studies and clinical trials for familial adenomatous polyposis (FAP) patients supported the possibility that NSAIDs can be used as chemopreventive agents. The major target molecules of NSAIDs are cyclooxygenases (COX), which catalyze the rate-limiting step of prostaglandin biosynthesis. Two isoenzymes of COX have been identified: COX-1 and COX-2. Whereas COX-1 is expressed constitutively in most tissues and responsible for tissue homeostasis, COX-2 is inducible and plays an important role in inflammation and tumorigenesis. A genetic study using compound mutant mice of COX-2−/− and ApcΔ716, a model for human familial adenomatous polyposis (FAP), directly demonstrated that induction of COX-2 is critical for intestinal polyp formation. Numerous studies have also demonstrated that COX-2-selective inhibitors suppress intestinal polyp formation in Apc gene-mutant mice and xenografted cancer cell growths. In addition, stimulation of angiogenesis is one of the major effects by COX-2 expression that is induced in the polyp stromal cells. These data from animal model studies should be helpful in understanding the in vivo mechanism(s) of tumor suppression by NSAIDs or COX-2 inhibitors. Here, we review the animal studies that reported the suppression of intestinal tumor growths by NSAIDs or COX-2 inhibitors.<br>

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