Journal
CANCER LETTERS
Volume 251, Issue 2, Pages 268-277Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2006.11.032
Keywords
celecoxib; gastric cancer cell; apoptosis; Akt; GSK3 beta; NAG-1
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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 Scr9 GSK3 beta phosphorylation and induced upregulation of nonsteroidal anti-inflammatory drugs-activated gene-1 (NAG-1) expression. The effects of celecoxib on NAG-I expression were abolished by pretreatment with GSK3 beta inhibitor, SB216763. Furthermore, GSK3 beta gene silencing by siRNA inhibited the celecoxib-induced NAG-I expression. Our study demonstrated that Akt/GSK3 beta/NAG-1 signal pathway may represent as the major mechanism of the COX-2-independent effects of celecoxib on gastric cancer cells. (C) 2006 Elsevier Ireland Ltd. All rights reserved.
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