Abstract:
: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 peptide-endostatin mimic-kringle 5 (AARP), consisting of MMP-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.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Wang H,Yang Z,Gu Jdoi
10.1158/1535-7163.MCT-14-0266subject
Has Abstractpub_date
2014-11-01 00:00:00pages
2674-87issue
11eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-14-0266journal_volume
13pub_type
杂志文章abstract::Resistance to paclitaxel-based therapy is frequently encountered in the clinic. The mechanisms of intrinsic or acquired paclitaxel resistance are not well understood. We sought to characterize the resistance mechanisms that develop upon chronic exposure of a cancer cell line to paclitaxel in the presence of the P-glyc...
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0237
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2002-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0288
更新日期:2018-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
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更新日期:2002-04-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2009-09-01 00:00:00
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更新日期:2010-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0276
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更新日期:2016-06-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0079
更新日期:2007-10-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0011
更新日期:2018-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0032
更新日期:2009-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章,评审
doi:10.1158/1535-7163.MCT-06-0141
更新日期:2006-08-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
doi:
更新日期:2001-11-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0657
更新日期:2018-04-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0580
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