Ginsenoside Rg3 inhibits HIF-1α and VEGF expression in patient with acute leukemia via inhibiting the activation of PI3K/Akt and ERK1/2 pathways

Int J Clin Exp Pathol. 2014 Apr 15;7(5):2172-8. eCollection 2014.

Abstract

Aberrant angiogenesis is essential to the development and progression of leukemia. Ginsenoside Rg3 has been commonly used in anti-angiogenic therapy of solid tumors. This study aimed to investigate the anti-angiogenic effects of Rg3 in patients with acute leukemia. Bone marrow stromal cells derived from patients with acute leukemia were treated with Rg3 and the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) was detected by RT-PCR and western blot analysis. The results showed that Rg3 inhibited VEGF and HIF-1α expression at both mRNA and protein levels in bone marrow stromal cells. In addition, Rg3 treatment led to reduced serum levels of HIF-1α and VEGF in patients with acute leukemia. Mechanistically, we demonstrated that Rg3 downregulated the phosphorylation of Akt and ERK1/2 in BMSCs. In conclusion, Rg3 exhibits anti-leukemia effect in part due to its anti-angiogenic activity via inhibiting PI3K/Akt and ERK1/2 pathways, which act to regulate the expression of HIF-1α and VEGF.

Keywords: Acute leukemia; Rg3; angiogenesis; bone marrow stromal cells; hypoxia-inducible factor 1; vascular endothelial growth factor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiogenesis Inhibitors / therapeutic use*
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / enzymology
  • Bone Marrow Cells / pathology
  • Cells, Cultured
  • China
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Leukemic
  • Ginsenosides / therapeutic use*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Phosphorylation
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Stromal Cells / drug effects*
  • Stromal Cells / enzymology
  • Stromal Cells / pathology
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Ginsenosides
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • ginsenoside Rg3
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3