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.
Pubmed ID: 8945508 RIS Download
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