구강암 세포주에서 COX-2억제제에 의한 세포성장 억제 효과 및 세포사멸 기전 연구

Abstract

Recently, prostaglandins have been reported to influence cell proliferation resulting in cancer development and progression. Prostaglandins are synthesized by cyclooxygenase (COX) pathway, COX-1 is constituently present in most cells and tissues where produce prostaglandins, while COX-2 expression is a critical part of inflammation and plays a major role in defending against exogenous stimuli. Moreover, COX-2 has been known to be related to cancer progression. Accordingly, cancer prevention trials have been applied by use of COX-2 inhibitors. Several putative targets have been proposed to account for NSAID-induced growth inhibition and apoptosis. This study was aimed at investigating the growth inhibitory effect and apoptosis mechanism by selective COX-2 inhibitor, celecoxib, in human oral squamous carcinoma cancer (OCC) cell lines. As a results, Celecoxib inhibited the growth of the cell lines in a dose dependent manner. Cell cycle kinetic analysis demonstrated that Celcoxib induces a delay in cll cycle progression and a G1 arrest. This induction of a G1 arrest was associated with the up-regulation of cyclin dependent kinase inhibitors (CDKI) p27KIP1 and P21CIP/WAF1. In adddition, 70 uM Celecoxib induced apoptosis through caspase-3 pathway. In conclusion, this study indicates that COX-2 specific inhibitor celecoxib induces apoptosis and cell cycle arrest in two oral squamous carcinoma cell lines.