A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics

Cancer Res. 2004 May 15;64(10):3365-70. doi: 10.1158/0008-5472.CAN-03-2682.

Abstract

Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. We developed a novel VEGF blockade system using RNA interference. The small interfering RNA (siRNA) targeting human VEGF almost completely inhibited the secretion of VEGF in a human prostate cancer cell line, PC-3, whereas the control scramble siRNA showed no effects. The VEGF siRNA with atelocollagen dramatically suppressed tumor angiogenesis and tumor growth in a PC-3 s.c. xenograft model. Atelocollagen provided a beneficial delivering means by which stabilization and efficient transfection of the siRNA injected into the tumors were achieved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Collagen / administration & dosage
  • Gene Transfer Techniques
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / therapy*
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / therapy*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics*
  • Transfection
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • atelocollagen
  • Collagen