Document Detail

Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo.
MedLine Citation:
PMID:  20004446     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic member of the B cell lymphoma/leukemia-2 (Bcl-2) family, has been shown to be involved in apoptosis and the cell cycle. Mcl-1 is overexpressed in many malignancies, including pancreatic cancer. The aim of this study was to investigate the effect of siRNA targeted against Mcl-1 on the radiosensitivity of human pancreatic carcinoma cells. METHODS: In 3 pancreatic cancer cell lines, the expression of Mcl-1 mRNA was determined by RT-PCR assay, and the dose-dependent cytotoxicity of radiation was also assessed. Furthermore, the effects of adenovirus-mediated siRNA targeted against Mcl-1 on radiosensitivity of PANC-1 cells both in vitro and in vivo were evaluated. RESULTS: Pancreatic cancer cells showed various levels of Mcl-1 mRNA that were correlated with the radiosensitivity of tumor cells. AdU6/shMcl-1 significantly downregulated the expression of Mcl-1 gene in PANC-1 cells, the most radioresistant cell line. Furthermore, Mcl-1 downregulation could significantly enhance radiosensitivity of PANC-1 cells in vitro and in vivo. The mechanism might be correlated with apoptosis enhancement by activating celluar caspase-3. CONCLUSION: Mcl-1 might be a therapeutic target for radiosensitization of pancreatic carcinoma cells. Adenovirus-mediated siRNA targeting of Mcl-1 could enhance the radiosensitivity of pancreatic cancer cells both in vitro and in vivo, and thus might be a potential strategy for ameliorating cancer.
Xiang Guoan; Wang Hanning; Chen Kaiyun; Liu Hao
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Publication Detail:
Type:  Journal Article     Date:  2009-12-11
Journal Detail:
Title:  Surgery     Volume:  147     ISSN:  1532-7361     ISO Abbreviation:  Surgery     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-04-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-61     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 Mosby, Inc. All rights reserved.
Department of General Surgery, The Second People's Hospital of Guangdong Province, Guangzhou, China.
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MeSH Terms
Adenoviridae / genetics*
Cell Line, Tumor
Pancreatic Neoplasms / genetics*,  radiotherapy
Proto-Oncogene Proteins c-bcl-2 / genetics*,  radiation effects
RNA, Messenger / genetics
RNA, Neoplasm / genetics
RNA, Small Interfering / genetics*
Radiation Tolerance / radiation effects
Sarcoma, Myeloid / genetics
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/RNA, Small Interfering; 0/myeloid cell leukemia sequence 1 protein

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