DSGOST inhibits tumor growth by blocking VEGF/VEGFR2-activated angiogenesis

Oncotarget. 2016 Apr 19;7(16):21775-85. doi: 10.18632/oncotarget.7982.

Abstract

Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer.

Keywords: DSGOST; VEGF; angiogenesis; herbal medicine; tumor.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cells, Cultured
  • Drugs, Chinese Herbal / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / metabolism
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Signal Transduction / genetics
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Drugs, Chinese Herbal
  • NF-kappa B
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2