Document Detail


Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3beta/NAG-1 pathway.
MedLine Citation:
PMID:  17257745     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rui-Ping Pang; Jia-Guo Zhou; Zhi-Rong Zeng; Xiao-Yan Li; Wei Chen; Min-Hu Chen; Pin-Jin Hu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-25
Journal Detail:
Title:  Cancer letters     Volume:  251     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-07     Completed Date:  2007-07-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  268-77     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Apoptosis / drug effects
Caspase 3 / metabolism
Cell Line, Tumor
Collagen Type XI / metabolism
Cyclooxygenase 2 / deficiency*,  physiology
Cytokines / metabolism*
Gene Expression
Growth Differentiation Factor 15
Humans
Membrane Proteins / deficiency*,  physiology
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism*
Pyrazoles / pharmacology*
Repressor Proteins / metabolism*
Signal Transduction
Stomach Neoplasms / metabolism*
Sulfonamides / pharmacology*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/C14orf129 protein, human; 0/COL11A2 protein, human; 0/Collagen Type XI; 0/Cytokines; 0/GDF15 protein, human; 0/Growth Differentiation Factor 15; 0/Membrane Proteins; 0/Pyrazoles; 0/Repressor Proteins; 0/Sulfonamides; 169590-42-5/celecoxib; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspase 3

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