Antitumor treatment efficacy by targeting epidermal growth factor receptor and vascular endothelial growth factor receptor-2 in an orthotopic human glioblastoma model.

Abstract

Using an orthotopic intracerebral model from our established HM55-BGIV-101 tumor line, we investigated the antitumor effect on the angiogenesis and growth of human glioblastoma after treatment with monoclonal antibody DC101 against the vascular endothelial growth factor receptor-2 and monoclonal antibody C225 against the epidermal growth factor receptor. Nude mice bearing intracerebral glioblastoma xenografts were treated intraperitoneally with DC101 and C225 either alone or in combination. Histopathological analysis of solid tumor volume, satellite tumor number, microvessel density, tumor cell proliferation, and apoptosis was performed. In the DC101-treated group, solid tumor volume and microvessel density were reduced by 59.7 and 64%, respectively; tumor cell proliferative activity was reduced by 53.2% and the apoptotic index (AI) was increased by 66.7%; satellite tumor number was enhanced by 84.4%. C225 alone reduced satellite tumor number by 43.3%, but had no effect on solid tumor volume, microvessel density, tumor cell proliferation, and apoptosis. C225 combined with DC101 not only reduced solid tumor volume, microvessel density, tumor cell proliferative activity, and increased AI, but also reduced satellite tumor number. Inhibition of angiogenesis achieved by DC101 can cause increased tumor cell invasiveness. In our studies this increased tumor cell invasiveness was inhibited simultaneously by C225, which provides a theoretical basis for treatment of glioblastoma by the method of combining drugs with different pharmacological activity.

• Authors: Diao Yi, Tian Xin Hua, Huang Yan Lin, Chen Lu Kui, Lin Xiao Ning, Zhuang Zai Wang
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 104 Issue 1 Pg. 93-101 (Aug 2011) ISSN: 1573-7373 [Electronic] United States
• PMID: 21140283 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD34
• DC101 monoclonal antibody
• Protein Precursors
• Vascular Endothelial Growth Factor A
• epidermal growth factor precursor
• Epidermal Growth Factor
• Vascular Endothelial Growth Factor Receptor-2
• Cetuximab

Topics

• Analysis of Variance
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antigens, CD34 (metabolism)
• Brain Neoplasms (drug therapy, metabolism, mortality, pathology)
• Cell Proliferation (drug effects)
• Cetuximab
• Disease Models, Animal
• Epidermal Growth Factor (immunology, metabolism)
• Glioblastoma (drug therapy, metabolism, mortality, pathology)
• Humans
• In Situ Nick-End Labeling (methods)
• Male
• Mice
• Middle Aged
• Neoplasm Transplantation (methods)
• Protein Precursors (immunology, metabolism)
• Survival Analysis
• Time Factors
• Vascular Endothelial Growth Factor A (immunology, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (immunology, metabolism)