MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells

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• 作者：Jhy-Ming Li (1) (2)
  Kuo-Chin Kao (1)
  Li-Fu Li (1)
  Tsung-Ming Yang (3)
  Chean-Ping Wu (4)
  Yan-Ming Horng (4)
  William WG Jia (5)
  Cheng-Ta Yang (1) (6)
  
• 关键词：Oncolytic virus ; MicroRNA ; Lung cancer ; Radiotherapy
• 刊名：Virology Journal
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：10
• 期：1
• 全文大小：297KB
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• 作者单位：Jhy-Ming Li (1) (2)
  Kuo-Chin Kao (1)
  Li-Fu Li (1)
  Tsung-Ming Yang (3)
  Chean-Ping Wu (4)
  Yan-Ming Horng (4)
  William WG Jia (5)
  Cheng-Ta Yang (1) (6)
  
  1. Department of Thoracic Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, 333, Kragujevac, Taoyuan, Taiwan
  2. Graduate Institute of Animal Science, College of Agriculture, National Chiayi University, Chiayi, Taiwan
  3. Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
  4. Department of Animal Science, National Chiayi University, Chiayi, Taiwan
  5. Departments of Surgery, University of British Columbia, Vancouver, BC, Canada
  6. Department of Respiratory Therapy, Chang Gung University, Kragujevac, Taoyuan, Taiwan
  
• ISSN：1743-422X

文摘

Background Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and novel treatment modalities to improve the prognosis of patients with advanced disease are highly desirable. Oncolytic virotherapy is a promising approach for the treatment of advanced NSCLC. MicroRNAs (miRNAs) may be a factor in the regulation of tumor-specific viral replication. The purpose of this study was to investigate whether miRNA-145 regulated oncolytic herpes simplex virus-1 (HSV-1) can selectively kill NSCLC cells with reduced collateral damage to normal cells. Methods We incorporated 4 copies of miRNA-145 target sequences into the 3-untranslated region of an HSV-1 essential viral gene, ICP27, to create AP27i145 amplicon viruses and tested their target specificity and toxicity on normal cells and lung cancer cells in vitro. Results miRNA-145 expression in normal cells was higher than that in NSCLC cells. AP27i145 replication was inversely correlated with the expression of miRNA-145 in infected cells. This oncolytic HSV-1 selectively reduced cell proliferation and prevented the colony formation of NSCLC cells. The combination of radiotherapy and AP27i145 infection was significantly more potent in killing cancer cells than each therapy alone. Conclusions miRNA-145-regulated oncolytic HSV-1 is a promising agent for the treatment of NSCLC.