Potential utility of COX-2 inhibitors in chemoprevention and chemotherapy.
Increased prostaglandin (PG) production is associated with many inflammatory pathophysiological conditions; it is derived from arachidonic acid by either of two enzymes: cyclooxygenase-1 or -2 (COX-1 or COX-2). In addition to its role in inflammation, recent work suggests COX-2 derived prostaglandins may play a pivotal part in the maintenance of tumour viability, growth and metastasis. In this review, we summarise the non-steroidal anti-inflammatory drug (NSAID) epidemiological evidence, studies demonstrating overexpression of COX-2 in multiple human tumours and the pharmacological evidence in animal models which also support this hypothesis. We also discuss the potential functional roles of COX-2 activity during tumourigenesis, and speculate on the mechanism by which COX-2 inhibitors may exert their anticancer effects.
Koki
AT
Monsanto Corporate Research, Monsanto/Searle Discovery Research, 700 Chesterfield Parkway North, Mailzone BB3K, Chesterfield, MO 63017, USA. ATKOKI@monsanto.com
Leahy
KM
Masferrer
JL