ABSTRACT
Cyclooxygenase-2 (Cox2) is an inductible isoenzyme of cyclooxygenase undetectable in normal colonic mucosa and overexpressed in 80% colonic tumor. Several works in vitro and in vivo showed that Cox2 plays a key role in the multistep process of colorectal tumorigenesis such apoptosis inhibition of cellular proliferation and angiogenesis induction. So that Cox2 represent a potential molecular target in colorectal management and specific Cox2 inhibitors may be useful as chemopreventive as well as therapeutic agent in humans. In animals study Cox2 inhibitors was shown to be effective and in humans Cox2 inhibitors are approved by the Food and Drug Administration as an adjunct to endoscopic surveillance and surgery in patients with Familial Adenomatous Polyposis (FAP). The purpose of this article is to review the relationship between Cox2/Cox2 inhibitors and differents signaling pathways of colorectal carcinogenesis and to precise their possible molecular mechanisms of action. This work although review clinicals data of their efficacy as chemopreventive agent as well as therapeutic in the differents group at risk for colorectal cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/enzymology , Cyclooxygenase Inhibitors/therapeutic use , Isoenzymes/antagonists & inhibitors , Neoplasm Proteins/antagonists & inhibitors , Adenomatous Polyposis Coli/drug therapy , Animals , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Enterocolitis/complications , Enterocolitis/enzymology , Enzyme Induction , Humans , Isoenzymes/physiology , Membrane Proteins , Microsatellite Repeats/genetics , Models, Animal , Neoplasm Proteins/physiology , Neovascularization, Pathologic , Prostaglandin-Endoperoxide Synthases/physiology , Signal TransductionABSTRACT
Cyclooxygenase-2 (Cox2) is an inductible isoenzyme of cyclooxygenase undetectable in normal colonic mucosa and overexpressed in 80% colonic tumor. Several works in vitro and in vivo showed that Cox2 plays a key role in the multistep process of colorectal tumorigenesis such apoptosis inhibition of cellular proliferation and angiogenesis induction. So that Cox2 represent a potential molecular target in colorectal management and specific Cox2 inhibitors may be useful as chemopreventive as well as therapeutic agent in humans. In animals study Cox2 inhibitors was shown to be effective and in humans Cox2 inhibitors are approved by the Food and Drug Administration as an adjunct to endoscopic surveillance and surgery in patients with Familial Adenomatous Polyposis (FAP). The purpose of this article is to review the relationship between Cox2\Cox2 inhibitors and differents signaling pathways of colorectal carcinogenesis and to precise their possible molecular mechanisms of action. This work although review clinicals data of their efficacy as chemopreventive agent as well as therapeutic in the differents group at risk for colorectal cancer.
