Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2).
Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H2: constitutive COX-1 and inducible COX-2. To assess the role of COX-2 in colorectal tumorigenisis, we determined the effects of COX-2 gene (Ptgs2) knockouts and a novel COX-2 inhibitor on Apc delta716 knockout mice, a model of human familial adenomatous ... polyposis. A Ptgs2 null mutation reduced the number and size of the intestinal polyps dramatically. Furthermore, treating Apc delta716 mice with a novel COX-2 inhibitor reduced the polyp number more significantly than with sulindac, which inhibits both isoenzymes. These results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis and indicate that COX-2-selective inhibitors can be a novel class of therapeutic agents for colorectal polyposis and cancer.
Mesh Terms:
Adenomatous Polyposis Coli, Adenomatous Polyposis Coli Protein, Animals, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Cytoskeletal Proteins, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Extracellular Space, Female, Furans, Gene Dosage, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Genes, APC, Intestinal Mucosa, Isoenzymes, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutagenesis, Prostaglandin-Endoperoxide Synthases, Sulindac, Time Factors
Adenomatous Polyposis Coli, Adenomatous Polyposis Coli Protein, Animals, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Cytoskeletal Proteins, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Extracellular Space, Female, Furans, Gene Dosage, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Genes, APC, Intestinal Mucosa, Isoenzymes, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutagenesis, Prostaglandin-Endoperoxide Synthases, Sulindac, Time Factors
Cell
Date: Nov. 29, 1996
PubMed ID: 8945508
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