COX selectivity and animal models for colon cancer
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Updated: Sep 7, 2026
Orthotopic Mouse Model of Colorectal Cancer
Published on: December 4, 2007
Masanobu Oshima1, Makoto M Taketo
1Department of Pharmacology, Kyoto University Graduate School of Medicine, Yoshida-Kono cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Abstract:
Early experiments performed during 1980s and 1990s 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 intestinal tumorigenesis. A genetic study using compound mutant mice of COX-2(-)/(-), and Apc(Delta716) which is 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. On the other hand, another study indicated that COX-1 also plays an important role in the early stage of intestinal tumorigenesis. 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 have been published as of August 2001, and reported to suppress intestinal tumor growths by NSAIDs or COX-2 inhibitors.
Insights
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.
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