title: Recombinant IFN-α2a-NGR exhibits higher inhibitory function on tumor neovessels formation compared with IFN-α2a in vivo and in vitro.
abstract: We previously reported that NGR-fused IFN-α2a (IFN-α2a-NGR) exhibited similar biological activities with native IFN-α2a and was well-tolerated in mice, rats and monkeys. In the current study, we evaluated the mechanisms of this fusion protein on angiogenesis and tumor formation. Our data indicated that IFN-α2a-NGR has the ability to target tumor blood vessels while preserving the original function of native IFN-α2a. IFN-α2a-NGR was found to be concentrated in the tumor tissues, particularly around the vessel areas. In contrast to IFN-α2a, IFN-α2a-NGR significantly decreased microvessel density and increased the apoptosis of vascular endothelial cells. IFN-α2a-NGR also decreased the expression of VEGF and bFGF in tumor cells. Significant inhibition of invasion, migration, tube formation and induction of apoptosis of endothelial cells were observed in IFN-α2a-NGR-treated group. In conclusion, results from in vitro and in vivo experiments indicate that IFN-α2a-NGR is a promising anti-angiogenic agent with greater therapeutic efficacy than IFN-α2a.
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Weina
authors.initials: W
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Liqing
authors.initials: L
authors.lastname: He
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Jieru
authors.initials: J
authors.lastname: Meng
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratories of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. zhangyqh@fmmu.edu.cn.|Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, 17 Changle West Road, Xi'an, 710032, People's Republic of China. zhangyqh@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. Zhangw90@fmmu.edu.cn.|Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, 17 Changle West Road, Xi'an, 710032, People's Republic of China. Zhangw90@fmmu.edu.cn.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
keywords: Anti-tumor activity; IFN-α2a-NGR; NGR peptide; Tumor neovessels; Tumor-targeted IFN-a2a