NDLI: Preparation and functional characterization of human vascular endothelial growth factor-melittin fusion protein with analysis of the antitumor activity in vitro and in vivo.

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Preparation and functional characterization of human vascular endothelial growth factor-melittin fusion protein with analysis of the antitumor activity in vitro and in vivo.

Content Provider	Semantic Scholar
Author	Wang, Dingding Hu, Lili Su, Manman Wang, Ju Xu, Tianmin
Copyright Year	2015
Abstract	Vascular endothelial growth factor and its tyrosine kinase receptors have been identified as key mediators of the regulation of pathologic blood vessel growth and maintenance in the promotion of angiogenesis and tumor growth. Therefore, an alternative approach to destroying tumor endothelium would be to make this tissue particularly sensitive to VEGF-mediated drug delivery. To verify this hypothesis, we generated a protein containing VEGF165 fused to melittin. Melittin is a small linear peptide composed of 26 amino acid residues that can exert toxic or inhibitory effects on many types of tumor cells. This protein is a cytolytic peptide that attacks lipid membranes, leading to significant toxicity. In the present study, the Pichia pastoris expression system was used to express the fusion protein. Under optimal conditions, stable VEGF165-melittin production was achieved using a series of purification steps. The activity of VEGF165-melittin fusion protein was compared with melittin for its ability to suppress the growth of tumor cell line in vitro. The fusion toxin selectively inhibited growth of human hepatocellular carcinoma HepG-2 cell line with high expression of VEGFR-2. We found that sensitivity of VEGFR-2 transfected 293 cells to VEGF165-melittin enhanced as the cellular VEGFR-2 density increased. In an in vivo initial experiment, the fusion protein inhibited tumor growth in xenografts assays. Furthermore, successful expression and characterization of the fusion protein demonstrated its efficacy for use as a novel treatment strategy for cancer.
Starting Page	115102
Ending Page	115102
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://www.spandidos-publications.com/ijo/47/3/1160/download
PubMed reference number	26166416v1
Alternate Webpage(s)	https://doi.org/10.3892/ijo.2015.3078
DOI	10.3892/ijo.2015.3078
Journal	International journal of oncology
Volume Number	47
Issue Number	3
Language	English
Access Restriction	Open
Subject Keyword	Adverse reaction to drug Amino Acids Blood Vessel Cell Line, Tumor Drug Delivery Systems Endothelial Growth Factors Leukemia, B-Cell Liver carcinoma Melitten Neoplasms Protein Tyrosine Kinase Receptor Protein-Tyrosine Kinases Staphylococcal Protein A Tissue membrane VEGF165 protein, human Vascular Endothelial Growth Factor Receptor-2 Xenograft procedure chimeric protein
Content Type	Text
Resource Type	Article

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