Combination gene therapy using VEGF-shRNA and fusion suicide gene yCDglyTK inhibits gastric carcinoma growth

Exp Mol Pathol. 2011 Dec;91(3):745-52. doi: 10.1016/j.yexmp.2011.07.007. Epub 2011 Aug 7.

Abstract

Clinical trials of suicide gene therapy have achieved limited success, which suggests a need for improvement. Angiogenesis plays a crucial role in the progression of cancers, which is greatly regulated by vascular endothelial growth factor (VEGF).The current study was designed to evaluate the anti-tumor effects of VEGF siRNA in combination with fusion suicide gene yCDglyTK. Introduction of a VEGF-targeted small hairpin RNA (shVEGF) to CDTK/5-FC system could induce cell apoptosis more effectively and decrease micro vessel density in xenograft tissue, thus resulted in a significant tumor growth delay in SGC7901 xenografts. These findings for the first time suggest the potential of combination gene therapy using suicide gene therapy and anti-angiogenesis gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Female
  • Gene Fusion
  • Genes, Transgenic, Suicide*
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / therapy*
  • RNA Interference
  • RNA, Small Interfering*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Vascular Endothelial Growth Factor A / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A