Document Detail


Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation.
MedLine Citation:
PMID:  22504904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC).
METHODS: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1.
RESULTS: Celecoxib (10-75 μmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 μmol/L) induced apoptosis and cell-cycle arrest at the G(0)/G(1) checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 μmol/L).
CONCLUSION: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.
Authors:
Dong-bo Liu; Guang-yuan Hu; Guo-xian Long; Hong Qiu; Qi Mei; Guo-qing Hu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-16
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  33     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-04     Completed Date:  2012-08-28     Revised Date:  2013-05-14    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  United States    
Other Details:
Languages:  eng     Pagination:  682-90     Citation Subset:  IM    
Affiliation:
Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Cell Cycle Checkpoints / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin D1 / metabolism
Cyclooxygenase 2 / metabolism
Dose-Response Relationship, Drug
Flow Cytometry
Humans
Interleukin-6 / metabolism
Nasopharyngeal Neoplasms / metabolism*,  pathology
Phosphorylation
Protein Processing, Post-Translational / drug effects
Proto-Oncogene Proteins c-bcl-2 / metabolism
Pyrazoles / pharmacology*
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
Sulfonamides / pharmacology*
Time Factors
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/CCND1 protein, human; 0/IL6 protein, human; 0/Interleukin-6; 0/Proto-Oncogene Proteins c-bcl-2; 0/Pyrazoles; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Sulfonamides; 0/myeloid cell leukemia sequence 1 protein; 136601-57-5/Cyclin D1; 169590-42-5/celecoxib; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human
Comments/Corrections
Erratum In:
Acta Pharmacol Sin. 2013 Apr;34(4):581

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