Therapeutic Targeting of Angiogenesis with a Recombinant CTT   Peptide-Endostatin Mimic-Kringle 5 Protein

doi:10.1158/1535-7163.MCT-14-0266

CORC > 北京大学 > 生命科学学院

	Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide-Endostatin Mimic-Kringle 5 Protein
	Wang, Houbin ; Yang, Zhigang ; Gu, Jun
刊名	molecular cancer therapeutics
	2014
关键词	SELECTIVE GELATINASE INHIBITOR ENDOTHELIAL-CELLS TUMOR ANGIOGENESIS ANTITUMOR-ACTIVITY DRUG DISCOVERY IN-VITRO ANTIANGIOGENESIS ANGIOSTATIN METASTASIS PLASMINOGEN
DOI	10.1158/1535-7163.MCT-14-0266
英文摘要	Angiogenesis is required for tumor growth and metastasis, and targeting angiogenesis is a novel anticancer strategy. However, cancer development is a complex multistep process, and single antiangiogenic agents have limited therapeutic efficacy. Here, we report a triple fusion protein, namely CTT peptideendostatin mimic-kringle 5 (AARP), consisting ofMMP-2/9-selective inhibitory peptide (CTT peptide) and well-known endogenous antiangiogenic agents (endostatin mimic and kringle 5), which can simultaneously target matrix metalloproteinases (MMP) and endothelial cells, blocking their actions. AARP was bacterially expressed, and biologic activity of purified AARP was assessed. AARP could significantly inhibit the enzymatic activity of MMP-2/9, proliferation, migration, and tube formation of endothelial cells in vitro. The antitumor activity of AARP was shown in a concentration-dependent manner when injected i.p. into immunodeficient mice bearing multidrug-resistant human epidermoid carcinomas (KB), and AARP is superior to clinical grade endostatin in inhibiting KB xenograft growth. In mouse models of Lewis lung carcinoma (LLC) and hepatoma H22, when given as a single dose, AARP is highly effective for reducing tumor growth, angiogenesis, and metastasis, and increasing survival time. AARP possessed significantly greater antiangiogenic activity than endostatin mimic, CTT peptide-kringle 5 (RK5) both in vitro and in vivo. Compared with conventional chemotherapeutic agents (cyclophosphamide and paclitaxel), AARP is also effective. More importantly, AARP is cytocompatible and no tissue toxicity could be observed after large dose administration. Taken together, our findings suggest AARP is a highly effective, safe, and more potent antiangiogenic agent for blocking tumor angiogenesis and metastasis, and warrants further testing for clinical applications. (C) 2014 AACR.; Oncology; SCI(E); PubMed; 0; ARTICLE; gj@pku.edu.cn; 11; 2674-2687; 13
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/342012]
专题	生命科学学院
推荐引用方式 GB/T 7714	Wang, Houbin,Yang, Zhigang,Gu, Jun. Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide-Endostatin Mimic-Kringle 5 Protein[J]. molecular cancer therapeutics,2014.
APA	Wang, Houbin,Yang, Zhigang,&Gu, Jun.(2014).Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide-Endostatin Mimic-Kringle 5 Protein.molecular cancer therapeutics.
MLA	Wang, Houbin,et al."Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide-Endostatin Mimic-Kringle 5 Protein".molecular cancer therapeutics (2014).