Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol.

risk of esophageal cancer. To perform this, it is necessary to understand the potential mechanism(s) of esophageal carcinogenesis. Until now, several hypotheses have been postulated, with the main hypotheses being the link between cancer and prostaglandin E2 (PGE2). Based on many current studies, overexpression of COX-2 and elevation of COX-2-mediated PGE2 synthesis are thought to be associated with human esophageal carcinogenesis. COX-2 expression is up-regulated in several types of human cancers, including esophageal cancer (1). It also was observed that overexpression of COX-2 was induced by NMBA in rat esophagi and significantly associated with esophageal tumorigenesis (2). Recent studies demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs), e.g. aspirin, inhibited both COX-1 and COX-2 (3), and longterm intake of aspirin was associated with an up to 90% decreased risk of developing esophageal cancer (4). Our previous paper determined that NMBA-induced rat esophageal tumorigenesis was suppressed by JTE-522 (4-[4-cyclohexyl-2methyloxazol-5-yl]-2-fluorobenzenesulfonamide), a selective COX-2 inhibitor, by decreasing COX-2-mediated PGE2 without reduction of COX-2 expression (2). Thus, suppression of COX-2 expression and/or the COX-2-mediated PGE2 may be effective targets in chemoprevention of esophageal carcinogenesis.