A novel recombinant slow-release TNF α-derived peptide effectively inhibits tumor growth and angiogensis

Scientific Reports
Yi MaAn Hong

Abstract

RMP16, a recombinant TNF α-derived polypeptide comprising a specific human serum albumin (HSA)-binding 7-mer peptide identified by phage display screening (WQRPSSW), a cleavage peptide for Factor Xa (IEGR), and a 20-amino acid bioactive peptide P16 (TNF α segment including amino acid residues 75-94), was prepared by gene-engineering technology. RMP16 showed prolonged half-life, 13.11 hours in mice (half-lives of P16 and TNF α are 5.77 and 29.0 minutes, respectively), and obviously higher receptor selectivity for TNFRI than TNF α. RMP16 had significant inhibition effects for multiple tumor cells, especially prostate cancer Du145 cells, and human vascular endothelial cells but not for human mammary non-tumorigenic epithelial cells. RMP16 can more effectively induce apoptosis and inhibit proliferation for DU145 cells than P16 and TNF α via the caspase-dependent apoptosis pathway and G0/G1 cell cycle arrest. In nude mice with transplanted tumor of DU145 cells, RMP16 significantly induced apoptosis and necrosis of tumor tissues but causing less side effects, and tumor inhibitory rate reached nearly 80%, furthermore, RMP16 can potently inhibit tumor angiogenesis and neovascularization. These findings suggest that RMP16 may represent ...Continue Reading

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Citations

Jan 7, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Min ZhengXiaohong Xie
Aug 31, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiuxia YanYi Ma
Apr 6, 2021·Bioactive Materials·Yujun ZengKui Luo
May 1, 2021·Pharmaceutics·Artur ŚwierczekElżbieta Wyska
Jul 15, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Julia LarssonMats Jirstrand

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Methods Mentioned

BETA
phage display
sandwich immunoassay
electrophoresis
surface
isothermal titration calorimetry
fluorescence microscopy
chip
enzyme-linked immunosorbent assay
PCR
gel filtration

Software Mentioned

SPSS
Image J
WinNonlin

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