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PMID:8945508
| Citation |
Oshima, M, Dinchuk, JE, Kargman, SL, Oshima, H, Hancock, B, Kwong, E, Trzaskos, JM, Evans, JF and Taketo, MM (1996) Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87:803-9 |
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| Abstract |
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. |
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| Keywords |
Adenomatous Polyposis Coli/drug therapy; Adenomatous Polyposis Coli/enzymology; Adenomatous Polyposis Coli/genetics; Adenomatous Polyposis Coli Protein; Animals; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors/pharmacology; Cytoskeletal Proteins/genetics; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors/pharmacology; Extracellular Space/physiology; Female; Furans/pharmacology; Gene Dosage; Gene Expression Regulation, Enzymologic/physiology; Gene Expression Regulation, Neoplastic/physiology; Genes, APC/physiology; Intestinal Mucosa/enzymology; Intestinal Mucosa/pathology; Isoenzymes/drug effects; Isoenzymes/genetics; Isoenzymes/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis/physiology; Prostaglandin-Endoperoxide Synthases/drug effects; Prostaglandin-Endoperoxide Synthases/genetics; Prostaglandin-Endoperoxide Synthases/metabolism; Sulindac/pharmacology; Time Factors |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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