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

• Published in: Scientific reports Vol. 5; no. 1; p. 13595
• Main Authors: Ma, Yi, Zhao, Shaojun, Shen, Shutao, Fang, Shixiong, Ye, Zulu, Shi, Zhi, Hong, An
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.09.2015; Nature Publishing Group
• Subjects: 631/67/1059/153; 692/700/565/1436/152; Cell Line, Tumor; Cell Proliferation - drug effects; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Humanities and Social Sciences; Humans; multidisciplinary; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - pathology; Peptides - administration & dosage; Peptides - chemistry; Peptides - genetics; Recombinant Proteins - administration & dosage; Recombinant Proteins - chemistry; Science; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13595

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 a promising long-lasting antitumor therapeutic peptide with less TNF α-induced toxicity.