A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model

• Published in: Journal of Zhejiang University. B. Science 2008-08, Vol.9 (8), p.602-609
• Main Authors: Huang, Feng-ying, Li, Yue-nan, Wang, Hua, Huang, Yong-hao, Lin, Ying-ying, Tan, Guang-hong
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cancer therapies; Cell Line, Tumor; Cloning, Molecular; Colonic Neoplasms - blood supply; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Disease Models, Animal; Disease Progression; Gene Expression; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmids - genetics; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; Recombinant Fusion Proteins - therapeutic use; Thromboplastin - genetics; Thromboplastin - isolation & purification; Thromboplastin - metabolism; Thromboplastin - therapeutic use; Thrombosis - drug therapy; Thrombosis - pathology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - isolation & purification; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor A - therapeutic use; 组织因子; 肿瘤学; 血栓形成; 血管内皮生长因子
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B0820120

Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor （VEGF） and tissue factor （TF） to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction （RT-PCR）, and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF （rVEGF-TF） was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment （P〈0.05）, and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.