COX-2, NSAIDs and human neoplasia. Part I: Colorectal neoplasms.
Cyclooxygenase-2 (COX-2), the inducible cyclooxygenase isozyme involved in the conversion of arachidonic acid (AA) to biologically active prostanoids, has become the subject of intense interest during the last few years. The recent surge of interest stems from seminal studies that correlated elevated expression of COX-2 with tumor induction and progression, and epidemiological studies that correlated reduced risk of developing certain types of cancers with chronic use of non-steroidal anti-inflammatory agents (NSAIDs). Although these observations were first reported with colorectal cancer (CRC), similar findings have subsequently been made with other types of cancers. A wide spectrum of studies continue to be undertaken in both laboratory and clinical settings to elucidate the mechanisms underlying these anti-tumor effects of COX-2 for potential translation into cancer chemoprevention and therapy. The aim of this article is to present a review of COX genes, the prostaglandin-cyclooxygenase relationship, the role of COX-2 in carcinogenesis and the rationale for targeting COX-2 with NSAIDs for cancer chemoprevention. Special emphasis is given to the role of COX-2 expression in the genesis and progression of colorectal neoplasia, and its correlation with other pathological characteristics of CRC. Preliminary observations on COX-2 expression in inflammatory bowel disease (IBD)-related colorectal neoplasia are also presented.
Nasir
A
A
International Society for the Study of Comparative Oncology Inc., Silver Spring, Maryland 20901, USA.
Fernandez
P M
PM
Chughtai
O R
OR
Kaiser
H E
HE
D000236:Adenoma / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods; D003106:Colon / Q000201:enzymology; D003109:Colonic Diseases, Functional / Q000150:complications / Q000201:enzymology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D012007:Rectum / Q000201:enzymology; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases