Effects of curcumin on tumor angiogenesis and biomarkers, COX-2 and VEGF, in hepatocellular carcinoma cell-implanted nude mice

Clin Hemorheol Microcirc. 2006;34(1-2):109-15.


Anti-angiogenic activity of curcumin and effects of curcumin on angiogenic biomarkers, cycloxygenase (COX)-2 and vascular endothelial growth factor (VEGF) levels were investigated. One day after hepatocellular carcinoma cell (HepG2) cells (30 microl of 2 x 10(6) cells) were inoculated onto the upper layer of the skin-fold chamber (HepG2-group, n = 15), curcumin solutions of 300 and 3000 mg/kg BW were daily oral fed to HepG2-Cur-300 and HepG2-Cur-3000 groups (n = 30), respectively. Intravital fluorescence videomicroscopy was performed to monitor neocapillaries in the tumor on days 3, 7 and 14 post-tumor-inoculation, using RITC-dextran (0.1 ml of 0.5% injected intravenously). The tumor neocapillary density (NCD) was evaluated in correlation with the tumor area, using a digital image analysis. The results demonstrated that the NCD of HepG2-groups were significantly increased on day 7 and 14, compared to the aged-matched Sham-groups (p<0.001). The increased NCD on day 7 and 14 were attenuated significantly by daily treatment of curcumin solution (3000 mg/kg BW).The curcumin treatment reduced the tumor-induced over-expression of COX-2 and serum VEGF in HepG2 groups significantly (p<0.001), indicating that curcumin could inhibit tumor angiogenesis. This mechanism might be mediated through reduction of angiogenic biomarkers, COX-2 and VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors
  • Animals
  • Biomarkers / analysis
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / drug therapy*
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Cyclooxygenase 2 / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / drug therapy*
  • Membrane Proteins / genetics*
  • Mice
  • Microscopy, Video
  • Neovascularization, Pathologic / drug therapy*
  • Time Factors
  • Vascular Endothelial Growth Factor A / genetics*


  • Angiogenesis Inhibitors
  • Biomarkers
  • Membrane Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Curcumin