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COX-2 and prostanoid receptors: good targets for chemoprevention
Toshihiko Kawamori1, Keiji Wakabayashi
1Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan. tkawamor@gan2.ncc.go.jp
Abstract:
Accumulating evidence indicates that COX-2 inhibitors are involved in colon and breast cancer development. Our previous studies indicated that nimesulide and celecoxib, selective COX-2 inhibitors, show inhibitory effects of intestinal carcinogenesis in azoxymethane-treated rats and mice and in Min mice models. We recently found that nimesulide suppressed PhIP-induced breast cancer in female SD rats in which COX-2 protein was overexpressed. These results led us to investigate the effects of prostaglandin E2 (PGE2) in the target tissues. PGE2 showed its biological activity through binding to its membrane receptors, EP(1 to approximately 4). We also investigated the effects of EP receptors on colon carcinogenesis. We used receptor knockout mice and selective receptor antagonists. Our results indicated that the EP1 receptor plays a pivotal role in colon carcinogenesis. Selective EP1 receptor antagonists may be a new class of chemopreventive agents against colon cancer.
Insights
Selective COX-2 inhibitors show promise in preventing colon and breast cancer. Research indicates the EP1 receptor plays a key role in colon cancer development, suggesting EP1 antagonists as potential chemopreventive agents.
Area of Science:
- Oncology
- Pharmacology
- Gastroenterology
Background:
- Cyclooxygenase-2 (COX-2) inhibitors have been implicated in colon and breast cancer development.
- Previous studies demonstrated the inhibitory effects of selective COX-2 inhibitors (nimesulide, celecoxib) on intestinal carcinogenesis.
- Nimesulide was found to suppress PhIP-induced breast cancer in rats with overexpressed COX-2.
Purpose of the Study:
- To investigate the role of prostaglandin E2 (PGE2) and its receptors (EP1-4) in colon carcinogenesis.
- To evaluate the potential of EP1 receptor antagonists as chemopreventive agents for colon cancer.
Main Methods:
- Utilized receptor knockout mice models.
- Administered selective EP receptor antagonists.
- Examined the effects of EP receptors on colon carcinogenesis.
Main Results:
- The EP1 receptor was identified as playing a pivotal role in colon carcinogenesis.
- Selective EP1 receptor antagonists demonstrated potential in preventing colon cancer development.
Conclusions:
- The EP1 receptor is a critical factor in the development of colon cancer.
- Selective EP1 receptor antagonists represent a promising new class of chemopreventive agents for colon cancer.