Cyclooxygenase-2 expression in human esophageal carcinoma

On the basis of epidemiological observations that nonsteroidal antiinflamma tory drugs reduce the risk of esophageal carcinoma, we studied the expressi on of cyclooxygenase-2 (COX-2) in esophageal squamous cell carcinomas (SCCs ; n = 172) and in esophageal adenocarcinomas (ADCs; n = 27). Using immunohi stochemistry, we observed COX-2 expression in 91% of the SCCs and in 78% of the ADCs. Western blot analysis showed enhanced expression of the COX-2 pr otein in some tumors as compared with normal esophageal squamous epithelium , whereas similar amounts of the COX-1 protein were found in normal and can cerous tissues. COX expression was also studied in two esophageal cancer ce ll lines (OSC-1 and OSC-2) to evaluate the functional relevance of COX-2-de rived prostaglandins (PGs), OSC-2 cells expressed COX-2 but not COX-I, wher eas OSC-1 cells expressed high levels of COX-I but showed only a very weak COX-2 expression. Accordingly, PGE, synthesis was 600 times higher in the O SC-2 cells as compared with the OSC-1 cells. Treatment of OSC-2 cells with the selective COX-2 inhibitors flosulide and NS-398 concentration dependent ly suppressed PGE, synthesis and proliferation and also induced apoptosis. In contrast, no effect of the COX-2 inhibitors was seen in OSC-1 cells. Our data demonstrate that COX-2 is expressed in the majority of esophageal SCC s and ADCs and that COX-2-derived PGs play an important role in the regulat ion of proliferation and apoptosis of esophageal tumor cells. It is conclud ed that inhibition of COX-2 may be useful in the therapy of esophageal canc er.