首页|siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin

siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin

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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 dsplatin.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 cydin D1,and enhances chemoresistance in esophageal cancer cells.

TC21Esophageal squamous cell carcinomasiRNACisplatinChemosensitivity

Md.Raghibul Hasan、Shyam Singh Chauhan、Rinu Sharma、Ranju Ralhan

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Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029 , India

Department of Biotechnology, School of Biotechnology, Guru Gobind Singh Indraprastha University, New Delhi 110075, India

Department of Otolaryngology-Head and Neck Surgery, Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada

Department of Pathology and Laboratory Medicine, Alex Simona Shnaider Laboratory for Molecular Oncology, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada

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2012

10.3748/wjg.v18.i31.4127

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(31)
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