Document Detail


Survivin downregulation by siRNA/cationic liposome complex radiosensitises human hepatoma cells in vitro and in vivo.
MedLine Citation:
PMID:  20470195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate the effect of survivin-short hairpin RNA (shRNA) on the proliferation, apoptosis and radiosensitivity of human hepatoma SMMC-7721 cells. MATERIALS AND METHODS: Survivin-targeted small interfering RNA (siRNA) expression vector was constructed and transfected into SMMC-7721 cells mediated by cationic liposome. Survivin mRNA and protein expression were analysed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle and apoptosis were measured by flow cytometry (FCM) assay. Radiosensitivity of SMMC-7721 cells was examined using a colony-forming assay. Mice subcutaneously implanted with SMMC-7721 cells were monitored for tumour growth and survival after treatment, and tumours were analysed for proliferation, apoptosis, and angiogenesis biomarkers by immunohistochemistry staining. RESULTS: After transfection, the mRNA and protein expression of survivin gene in SMMC-7721 cells downregulated, which led to significant cell growth inhibition, cell arrest in G2/M phase, increased apoptotic rate and radiosensitivity. Survivin-shRNA in combination with radiotherapy was more effective than radiotherapy or survivin-shRNA therapy alone in suppressing tumour growth and extending survival duration. Combined therapy inhibited cell proliferation and tumour angiogenesis and increased apoptosis in tumour xenografts. CONCLUSION: Survivin downregulation by siRNA/cationic liposome inhibited proliferation, induced apoptosis and enhanced radiosensitivity in human hepatoma cells in vitro and in vivo.
Authors:
Wei Yang; Ting Sun; Jianping Cao; Fenju Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of radiation biology     Volume:  86     ISSN:  1362-3095     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  445-57     Citation Subset:  IM; S    
Affiliation:
Department of Radiobiology, School of Radiological Medicine and Public Health, Soochow University, Suzhou, China. detachedy@yahoo.com.cn
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics,  radiation effects
Base Sequence
Carcinoma, Hepatocellular / genetics,  pathology*,  physiopathology,  radiotherapy*
Caspase 3 / metabolism
Cell Cycle / genetics,  radiation effects
Cell Line, Tumor
Cell Proliferation / radiation effects
Down-Regulation / genetics*
Female
Gene Expression Regulation, Neoplastic / genetics,  radiation effects
Gene Silencing
Humans
Liposomes
Mice
Microtubule-Associated Proteins / deficiency*,  genetics*,  metabolism
Neovascularization, Pathologic / genetics,  radiotherapy
RNA, Small Interfering / administration & dosage,  genetics*
Radiation Tolerance / genetics*
Survival Analysis
X-Rays
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Liposomes; 0/Microtubule-Associated Proteins; 0/RNA, Small Interfering; EC 3.4.22.-/Caspase 3

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