[HTML][HTML] Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2)
M Oshima, JE Dinchuk, SL Kargman, H Oshima… - Cell, 1996 - cell.com
Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H
2: 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 Δ716 knockout mice, a model of human familial adenomatous polyposis.
A Ptgs2null mutation reduced the number and size of the intestinal polyps dramatically.
Furthermore, treating Apc Δ716 mice with a novel COX-2 inhibitor reduced the polyp number …
2: 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 Δ716 knockout mice, a model of human familial adenomatous polyposis.
A Ptgs2null mutation reduced the number and size of the intestinal polyps dramatically.
Furthermore, treating Apc Δ716 mice with a novel COX-2 inhibitor reduced the polyp number …
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 ApcΔ716knockout mice, a model of human familial adenomatous polyposis. A Ptgs2null mutation reduced the number and size of the intestinal polyps dramatically. Furthermore, treating ApcΔ716mice 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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