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COX selectivity and animal models for colon cancer
Masanobu Oshima1, Makoto M Taketo
1Department of Pharmacology, Kyoto University Graduate School of Medicine, Yoshida-Kono cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Current Pharmaceutical Design
|April 12, 2002
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors show promise in preventing intestinal tumors. Animal studies confirm their efficacy in suppressing polyp formation and tumor growth.
Area of Science:
- Gastroenterology
- Oncology
- Pharmacology
Background:
- Non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated inhibitory effects on intestinal tumorigenesis in animal models.
- Epidemiological studies and clinical trials in familial adenomatous polyposis (FAP) patients suggest NSAIDs as potential chemopreventive agents.
- Cyclooxygenases (COX), specifically COX-1 and COX-2, are key targets of NSAIDs, involved in prostaglandin biosynthesis.
Purpose of the Study:
- To review animal studies investigating the efficacy of NSAIDs and COX-2 inhibitors in suppressing intestinal tumor growth.
- To elucidate the role of COX-1 and COX-2 in intestinal tumorigenesis based on animal model data.
- To understand the in vivo mechanisms of tumor suppression by NSAIDs and COX-2 inhibitors.
Main Methods:
- Review of published animal studies (as of August 2001) on NSAIDs and COX-2 inhibitors' effects on intestinal tumors.
- Analysis of carcinogen-induced rat intestinal tumor models.
- Examination of genetic studies using COX-2 knockout and Apc gene-mutant mice (FAP models).
Main Results:
- NSAIDs demonstrated inhibitory effects on intestinal tumorigenesis in early experimental models.
- COX-2 induction is critical for intestinal polyp formation, as shown in Apc(Delta716) mutant mice.
- Selective COX-2 inhibitors suppressed intestinal polyp formation in Apc gene-mutant mice and xenografted cancer cells.
- COX-2 expression in polyp stromal cells stimulates angiogenesis.
- COX-1 also plays a role in the early stages of intestinal tumorigenesis.
Conclusions:
- Animal model studies provide valuable insights into the in vivo mechanisms of NSAID and COX-2 inhibitor-mediated tumor suppression.
- COX-2 plays a critical role in intestinal polyp formation and growth, making it a key target for chemoprevention.
- Further research into the roles of both COX-1 and COX-2 is essential for understanding and developing effective intestinal cancer prevention strategies.