VEGF-specific siRNAs modified with 2-deoxy effectively suppress VEGF expression and inhibit growth of nasopharyngeal carcinoma xenograft in a mouse model

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• 作者：ShanYi Chen (1)
  GuoFeng Gao (1)
  Wei Chen (1)
  Qing Lü (2)
  Shen Tang (2)
  Zhong Hua (2)
  WenBin Ye (2)
  DaYong Gu (2)
  ShaYan Wang (1)
  YaOu Zhang (2)
  
• 关键词：small interfering RNA ; vascular endothelial growth factor (VEGF) ; nasopharyngeal carcinoma ; 2-deoxy modification ; ultrasound
• 刊名：Science China Life Sciences
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：51
• 期：2
• 页码：104-110
• 全文大小：2475KB
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• 作者单位：ShanYi Chen (1)
  GuoFeng Gao (1)
  Wei Chen (1)
  Qing Lü (2)
  Shen Tang (2)
  Zhong Hua (2)
  WenBin Ye (2)
  DaYong Gu (2)
  ShaYan Wang (1)
  YaOu Zhang (2)
  
  1. Shenzhen People’s Hospital, Clinical Medical College of Jinan University, Shenzhen, 518020, China
  2. Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, China
  

文摘

Vascular endothelial growth factor (VEGF) is up-regulated in the vast majority of human tumors. The up-regulation of VEGF not only plays important roles in tumor angiogenesis, but also provides a target for tumor treatment with small interfering RNA (siRNA) that targets VEGF; however, it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF. A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line. In this study, we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells, and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents. CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs. The expression of VEGF was effectively suppressed by VEGF-specific siRNAs, measured by ELISA, Western blot analysis and RT-PCR. Furthermore, experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells. VEGF-specific siRNAs were modified with 2-deoxy, then injected into the tumors, and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs. Tumor growth was reduced significantly after 3 weeks-treatment. These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression, such as CNE, and VEGF-specific siRNAs modified with 2-deoxy can be used as potential agents for tumor therapy.