Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model

Eur J Cancer. 2002 May;38(8):1133-40. doi: 10.1016/s0959-8049(02)00013-8.


We hypothesised that the combination of anti-angiogenic and anti-epidermal growth factor (EFG)-receptor (R) therapies would more effectively inhibit gastric cancer growth than single-agent therapy. TMK-1 gastric cancer cells were injected into the gastric wall of nude mice to generate tumours. After 4 days, mice were randomly assigned to the following groups: control, DC101 ([vascular endothelial growth factor (VEGF)-receptor (R)-2 antibody], C225 (EGF-R antibody), or a combination of DC101 and C225. The combination therapy significantly inhibited gastric tumour growth compared with the control group, whereas the decrease in tumour growth in mice treated with DC101 or C225 alone did not reach statistical significance. All mice administered DC101 demonstrated decreased tumour vascularity and increased endothelial cell apoptosis. C225 alone did not affect angiogenesis, but inhibited tumour cell proliferation. The combination therapy led to a further decrease in tumour cell proliferation. The combination of anti-VEGF-R and anti-EGF-R therapies was effective in inhibiting gastric cancer growth. These findings support the hypothesis that inhibiting multiple biological pathways that mediate tumour growth may be an effective therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Cell Division
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / prevention & control
  • Random Allocation
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptors, Growth Factor / antagonists & inhibitors*
  • Receptors, Growth Factor / immunology
  • Receptors, Vascular Endothelial Growth Factor
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / drug therapy*
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Receptors, Growth Factor
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor