Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3β/NAG-1 pathway

In this study, we analyzed the mechanisms of the apoptotic effects of celecoxib on COX-2 deficient gastric cancer cell line, MGC-803. We found celecoxib treatment induced caspase-dependent apoptosis in MGC-803 cells. Celecoxib inhibited Ser473 Akt and Ser9 GSK3β phosphorylation and induced upregulation of nonsteroidal anti-inflammatory drugs-activated gene-1 (NAG-1) expression. The effects of celecoxib on NAG-1 expression were abolished by pretreatment with GSK3β inhibitor, SB216763. Furthermore, GSK3β gene silencing by siRNA inhibited the celecoxib-induced NAG-1 expression. Our study demonstrated that Akt/GSK3β/NAG-1 signal pathway may represent as the major mechanism of the COX-2-independent effects of celecoxib on gastric cancer cells.