Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2).

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.
Authors	M Oshima, J E Dinchuk, S L Kargman, H Oshima, B Hancock, E Kwong, J M Trzaskos, J F Evans, M M Taketo
Journal	Cell (Cell) Vol. 87 Issue 5 Pg. 803-9 (Nov 29 1996) ISSN: 0092-8674 [Print] United States
PMID	8945508 (Publication Type: Journal Article)
Chemical References	Adenomatous Polyposis Coli Protein Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Cytoskeletal Proteins Enzyme Inhibitors Furans Isoenzymes 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone Sulindac Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases
Topics	Adenomatous Polyposis Coli (drug therapy, enzymology, 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, pathology) Isoenzymes (drug effects, genetics, metabolism) Male Mice Mice, Inbred C57BL Mice, Knockout Mutagenesis (physiology) Prostaglandin-Endoperoxide Synthases (drug effects, genetics, metabolism) Sulindac (pharmacology) Time Factors

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