Oridonin exhibits anti-angiogenic activity in human umbilical vein endothelial cells by inhibiting VEGF-induced VEGFR-2 signaling pathway

Pathol Res Pract. 2020 Aug;216(8):153031. doi: 10.1016/j.prp.2020.153031. Epub 2020 May 28.

Abstract

Oridonin has been found to be a potential anti-angiogenesis agent. However, its functional targets and the underlying mechanisms are still vague. In vitro studies we found that oridonin not only inhibited VEGF-induced cell proliferation, migration and tube formation but also caused G2/M phase arrest and triggered cellular apoptosis in HUVECs. In mechanistic studies revealed that oridonin exhibited the anti-angiogenic potency, at least in part, through the down-regulation of VEGFR2-mediated FAK/MMPs, mTOR/PI3K/Akt and ERK/p38 signaling pathways which led to reduced invasion, migration, and tube formation in HUVECs. Our results could provide evidence that oridonin exerts strong anti-angiogenesis activities via specifically targeting VEGFR2 and its signaling pathway.

Keywords: Anti-angiogenesis; HUVECs; Oridonin; VEGF; VEGFR2.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Diterpenes, Kaurane / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Signal Transduction / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Diterpenes, Kaurane
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • oridonin
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2