Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3beta/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 GSK3beta 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 GSK3beta inhibitor, SB216763. Furthermore, GSK3beta gene silencing by siRNA inhibited the celecoxib-induced NAG-1 expression. Our study demonstrated that Akt/GSK3beta/NAG-1 signal pathway may represent as the major mechanism of the COX-2-independent effects of celecoxib on gastric cancer cells.
Pang
Rui-Ping
RP
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
Zhou
Jia-Guo
JG
Zeng
Zhi-Rong
ZR
Li
Xiao-Yan
XY
Chen
Wei
W
Chen
Min-Hu
MH
Hu
Pin-Jin
PJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D000068579:Celecoxib; D045744:Cell Line, Tumor; D024161:Collagen Type XI / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D055436:Growth Differentiation Factor 15; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency* / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D016207:Cytokines; C526140:GDF15 protein, human; C514503:GSKIP protein, human; D055436:Growth Differentiation Factor 15; D008565:Membrane Proteins; D011720:Pyrazoles; D012097:Repressor Proteins; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D000068579:Celecoxib