Cyclooxygenase (COX) enzymes catalyze the synthesis of prostaglandins (PGs) from arachidonic acid. There are two isoforms of COX, COX-1 and COX-2. While COX-1 is expressed constitutively and appears to be responsible for the production of prostaglandins (PGs) that control normal physiologic functions, expression of COX-2 is induced by various inflammatory and mitogenic stimuli such as cytokines, growth factors or tumor promoters. Numerous experimental studies suggest a relationship between COX-2 expression and carcinogenesis. For example, increased amounts of COX-2 have been observed in breast cancers that overexpress HER-2/neu. Furthermore, treatment with selective inhibitors of COX-2
reduced the formation of tongue, esophagal, intestinal, breast, skin, lung, and bladder tumors in experimental animals.