Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Apoptosis / drug effects
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Caspase 3 / metabolism
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Celecoxib
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Cell Line, Tumor
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Collagen Type XI / metabolism
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Cyclooxygenase 2 / deficiency*
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Cyclooxygenase 2 / physiology
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Cytokines / metabolism*
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Gene Expression
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Growth Differentiation Factor 15
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Humans
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Membrane Proteins / deficiency*
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Membrane Proteins / physiology
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Phosphorylation
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Proto-Oncogene Proteins c-akt / metabolism*
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Pyrazoles / pharmacology*
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Repressor Proteins / metabolism*
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Signal Transduction
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Stomach Neoplasms / metabolism*
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Sulfonamides / pharmacology*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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COL11A2 protein, human
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Collagen Type XI
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Cytokines
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GDF15 protein, human
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GSKIP protein, human
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Growth Differentiation Factor 15
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Membrane Proteins
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Pyrazoles
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Repressor Proteins
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Sulfonamides
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Cyclooxygenase 2
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PTGS2 protein, human
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Proto-Oncogene Proteins c-akt
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Caspase 3
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Celecoxib