A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model.
- Author:
Feng-ying HUANG
1
;
Yue-nan LI
;
Hua WANG
;
Yong-hao HUANG
;
Ying-ying LIN
;
Guang-hong TAN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Line, Tumor; Cloning, Molecular; Colonic Neoplasms; blood supply; drug therapy; pathology; Disease Models, Animal; Disease Progression; Gene Expression; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Plasmids; genetics; Recombinant Fusion Proteins; genetics; isolation & purification; metabolism; therapeutic use; Thromboplastin; genetics; isolation & purification; metabolism; therapeutic use; Thrombosis; drug therapy; pathology; Vascular Endothelial Growth Factor A; genetics; isolation & purification; metabolism; therapeutic use
- From: Journal of Zhejiang University. Science. B 2008;9(8):602-609
- CountryChina
- Language:English
- Abstract: 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.
