COX-2 and colon cancer.
The role of cyclooxygenase-2 (COX-2) in colorectal tumorigenesis in mice was studied by Oshima et al. to determine the effects of COX-2 gene knockouts and a new COX-2 inhibitor. In the study, heterozygous Apcdelta716 knockout mice, a mouse model of human familial adenomatous polyposis (FAP), were either crossed to COX-2 gene knockout mice, or fed chow containing the COX-2-selective inhibitor. Apcdelta716 litter mates were used as positive controls, which developed 652+/-198 (SD) polyps at 10 weeks. Introduction of a COX-2 gene mutation, or feeding with the COX-2-selective inhibitor to the Apcdelta716 knockout mice, reduced the number and size of intestinal polyps dramatically. The results provide direct genetic evidence that COX-2 plays a key role in tumorigenesis, and indicate that COX-2-selective inhibitors can be a new class of therapeutic agents for colorectal polyposis and cancer.
Taketo
M M
MM
Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. taketo@mol.f.u-tokyo.ac.jp
D011125:Adenomatous Polyposis Coli / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D005663:Furans / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology*; D017154:Stromal Cells / Q000201:enzymology; D013467:Sulindac / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D008565:Membrane Proteins; C102563:3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone; D013467:Sulindac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases