Mc-hES, a novel plasmid carrying human endostatin gene, inhibits nasopharyngeal carcinoma growth

• Published in: Cancer gene therapy Vol. 19; no. 2; pp. 110 - 117
• Main Authors: Xu, B-L, Yuan, L, Wu, J-X, Xu, N, Fang, W-J, Zhao, P, Huang, W-L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2012; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Carcinoma; Cell Growth Processes - genetics; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Diagnosis; DNA, Circular - administration & dosage; DNA, Circular - genetics; Endostatin; Endostatins - biosynthesis; Endostatins - genetics; Endothelial cells; Gene Expression; Gene Therapy; Genetic aspects; Genetic Therapy - methods; Genetic vectors; Genetic Vectors - genetics; Hep G2 Cells; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - physiology; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nasopharyngeal cancer; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - therapy; Neovascularization; original-article; Physiological aspects; Plasmids; Plasmids - genetics; Risk factors; Throat cancer; Transfection; Tumors; Umbilical vein; Xenograft Model Antitumor Assays; Xenografts; China; plasmid; nasopharyngeal carcinoma; minicircle DNA vector; endostatin; nonviral vector
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/cgt.2011.72

Conventional plasmids for gene therapy produce low-level and short-term gene expression. Here, we first created minicircle carrying endostatin (mc-hES) for measurement of transfection efficiency. Compared with pcDNA-hES, MC-mediated endostatin gene transfer in vitro resulted in seven-fold greater endostatin expression levels in transfected cells and inhibited the growth of Human umbilical vein endothelial cells (HUVEC) more efficiently. HUVEC cell migration and tube-formation assays suggested that MC-mediated endostatin gene has significant anti-migration and anti-tube-formation capacity than that in pcDNA-hES. In vivo experiments showed that after transfection, mc-hES inhibited the growth of nasopharyngeal carcinoma xenografts. The tumor inhibition rates of mc-hES and pcDNA-hES were 60.8% and 26.9%, respectively ( P <0.05). MC-mediated intratumoral endostatin expression in vivo was 2.2–17.9 times higher than pcDNA-hES in xenografted mice and lasted for 20 days. Our results suggest that minicircle DNA vectors might be a promising vector for biotherapy and should be further investigated.