Inhibitory effects of Yangzheng Xiaoji on angiogenesis and the role of the focal adhesion kinase pathway

Int J Oncol. 2012 Nov;41(5):1635-42. doi: 10.3892/ijo.2012.1627. Epub 2012 Sep 11.

Abstract

Angiogenesis is an essential event during the excessive growth and metastatic spread of solid tumours. Anti-angiogenic agents have become a new choice of therapy for patients with cancer. In the present study, we investigated the potential effect of Yangzheng Xiaoji, a traditional Chinese medicinal formula presently used in the treatment of several solid tumours including liver cancer and gastric cancer, on angiogenesis, in vitro. The human vascular endothelial cell line HECV was used. A Matrigel-based sandwich tubule formation assay was employed to assess in vitro angiogenesis, a colorimetric method for assessing in vitro cell growth. Electric cell-substrate impedance sensing (ECIS) was used to evaluate the adhesion and migration of endothelial cells. The effects on activation of focal adhesion kinase (FAK) were evaluated using western blotting and immunofluorescence methods. Yangzhen Xiaoji extract DME25 significantly inhibited tube formation (p=0.046 vs control). This was seen together with a concentration-dependent inhibition on cell-matrix adhesion and cellular migration. It was demonstrated that the focal adhesion kinase (FAK) inhibitor PF557328 had a significant synergistic effect on DME25-induced inhibition of cell adhesion, migration and tube formation. The study showed that DME25 inhibited the phosphorylation of FAK in endothelial cells. In conclusion, Yangzhen Xiaoji has a marked effect on angiogenesis, in vitro and that this effect is at least partly mediated by the focal adhesion kinase (FAK) pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drug Synergism
  • Drugs, Chinese Herbal / pharmacology*
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic / drug effects
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction / drug effects*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • Protein Kinase Inhibitors
  • yangzheng xiaoji
  • Focal Adhesion Protein-Tyrosine Kinases