Enhancement of chemotherapeutic drug-induced apoptosis by a cyclooxygenase-2 inhibitor in hypopharyngeal carcinoma cells

Our previous study demonstrated that cyclooxygenase-2 (COX-2) was overexpressed in human hypopharyngeal carcinoma. In this study, we tested the effect of a specific COX-2 inhibitor, NS398, on proliferation of hypopharyngeal cancer cells. Our results indicated that NS398 inhibited growth of hypopharyngeal cancer cells and this inhibition is associated with induction of G1 growth arrest. Western blot analysis showed that expression of G1 cyclins or cyclin-dependent kinases (CDKs) was not changed by NS398. On the contrary, NS398 significantly increased expression of CDK inhibitors p21Waf1 and p27Kip1. We also found that treatment of NS398 alone could not induce significant apoptosis in hypopharyngeal cancer cells. However, NS398 potently augmented chemotherapeutic drug-induced apoptosis. Caspase activation and DNA fragmentation were clearly detected in cancer cells pretreated with NS398 followed by chemotherapeutic drugs. Collectively, our results suggest that COX-2 inhibitors may suppress proliferation of hypopharyngeal cancer cells via induction of G1 growth arrest and may be useful in combination with chemotherapeutic drugs for the treatment of hypopharyngeal carcinoma.