Traditional Chinese Medicine (TCM) Astragalus Membranaceus and Curcuma Wenyujin Promote Vascular Normalization in Tumor-derived Endothelial Cells of Human Hepatocellular Carcinoma

Anticancer Res. 2019 Jun;39(6):2739-2747. doi: 10.21873/anticanres.13400.

Abstract

Background/aim: The aim of the present study was to investigate the vascular normalization effect of traditional Chinese medicine Astragalus membranaceus (AM) and Curcuma wenyujin (CW) on tumor-derived endothelial cells (TECs).

Materials and methods: TECs were isolated from the xenografted HCC cell line HepG2 expressing red fluorescent protein (RFP). The effect of AM and CW on TECs proliferation was measured using the CCK8 assay. The vascular normalization potential of AM and CW was assessed using a tube formation assay. Immunocytochemistry was performed to assess the effect of AM and CW on the expression of angiogenic maker CD34 and hypoxia-inducible factor HIF1a.

Results: The isolated TECs and endothelioma (EOMA) cells did not differ with regard to the expression levels of endothelial markers CD34, VEGFR-1, VEGFR-2, PDGFR-α and PDGFR-β. All AM, CW, AM+CW and Nintedanib (Nin) showed a dose-dependent increasing inhibition effect on either TECs or EOMA cells. AM, CW and AM+CW significantly reduced HIF1a expression, increased CD34 expression and enhanced endothelial network formation in TECs or EOMA cells compared to the control.

Conclusion: AM and CW promoted vascular normalization in tumor-derived endothelial cells of HCC, through increased expression of CD34 and reduced expression of HIF1a.

Keywords: Astragalus membranaceus; Curcuma wenyujin; HCC; agiogenesis; vascular normalization.

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism*
  • Astragalus propinquus / chemistry
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Curcuma / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hep G2 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / metabolism*
  • Medicine, Chinese Traditional
  • Mice
  • Neoplasm Transplantation
  • Signal Transduction / drug effects

Substances

  • Antigens, CD34
  • Drugs, Chinese Herbal
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit