Inhibition of gastric cancer angiogenesis by vector-based RNA interference for Raf-1

Cancer Biol Ther. 2005 Jan;4(1):113-7. Epub 2005 Jan 8.

Abstract

Tumor angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Raf-1 is involved in this process, and may be critical in regulating gene activation of several angiogenesis factors. To further define Raf-1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock-down gene expression of Raf-1 in gastric cancer cell line SGC7901 that expresses a high level of Raf-1. The protein level of Raf-1 in the SGC7901cells was decreased dramatically after transfection with a Raf-1 specific siRNA vector. Further study proved that, VEGF and HIF-1alpha, two angiogenesis promoting factors, were found to be downregulated. And we also find that Vector-based RNA interference for Raf-1 increases transfected gastric cell apoptosis and inhibits cellular proliferation. Our results suggest that Raf-1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting Raf-1.

MeSH terms

  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors
  • Humans
  • Neovascularization, Pathologic*
  • Plasmids
  • Proto-Oncogene Proteins c-raf / genetics*
  • Proto-Oncogene Proteins c-raf / physiology*
  • RNA Interference*
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / genetics*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins c-raf