COX-2 and colon cancer

Inflamm Res. 1998 Oct:47 Suppl 2:S112-6. doi: 10.1007/s000110050295.

Abstract

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.

MeSH terms

  • Adenomatous Polyposis Coli / enzymology
  • Adenomatous Polyposis Coli / pathology
  • Adenomatous Polyposis Coli / therapy
  • Animals
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / therapeutic use
  • Furans / therapeutic use
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • Stromal Cells / enzymology
  • Sulindac / therapeutic use

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Furans
  • Isoenzymes
  • Membrane Proteins
  • 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone
  • Sulindac
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases