Document Detail


siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin.
MedLine Citation:
PMID:  22919244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To determine the functional significance of TC21 in esophageal squamous cell carcinoma (ESCC).
METHODS: TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and transcripts were analyzed by reverse transcription-polymerase chain reaction and protein by Western blotting. We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assessing the phosphorylation status of its downstream targets, phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), protein kinase B (pAkt), nuclear factor-κB (NF-κB) and cyclinD1 using specific antibodies. Cell survival analysis after cisplatin treatment was carried out by cell viability assay and cell cycle analysis using flow cytometry.
RESULTS: TC21 knockdown in human ESCC cell line TE13 cells, showed only a marginal increase (14.2%) in cell death compared with control cells. The expressions of the signaling proteins PI3K and pAkt, transcription factor NF-κB, and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregulation, whereas the level of pPTEN, an antagonist of PI3K, was increased. In addition, we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin. Increased cell death (38.4%) was observed in cells treated with cisplatin after TC21 knockdown compared with cells which were treated with cisplatin alone (20% cell death).
CONCLUSION: Results suggest that TC21 mediates its effects via the PI3K-Akt pathway, NF-κB and cyclin D1, and enhances chemoresistance in esophageal cancer cells.
Authors:
Raghibul Hasan; Shyam Singh Chauhan; Rinu Sharma; Ranju Ralhan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-24     Completed Date:  2013-04-04     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  4127-35     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Carcinoma, Squamous Cell / metabolism,  pathology
Cell Line, Tumor
Cisplatin / pharmacology*
Cyclin D1 / metabolism
Down-Regulation / drug effects*,  genetics
Esophageal Neoplasms / metabolism,  pathology*
Gene Knockdown Techniques
Humans
Membrane Proteins / genetics,  metabolism*
Monomeric GTP-Binding Proteins / genetics,  metabolism*
NF-kappa B / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / pharmacology*
Signal Transduction / drug effects
Transfection
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Membrane Proteins; 0/NF-kappa B; 0/RNA, Small Interfering; 136601-57-5/Cyclin D1; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.6.1/RRAS2 protein, human; EC 3.6.5.2/Monomeric GTP-Binding Proteins; Q20Q21Q62J/Cisplatin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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