PBA2 exhibits potent anti-tumor activity via suppression of VEGFR2 mediated-cell proliferation and angiogenesis

被引:8
作者
Fang, Xiaona [1 ]
Xie, Hua [2 ]
Luo, Min [1 ]
Chen, Zhen [1 ]
Wang, Fang [1 ]
Li, Qingshan [3 ]
Wang, Xiaokun [1 ]
Ding, Jian [2 ]
Fu, Liwu [1 ]
机构
[1] Sun Yat Sen Univ, Guangdong Esophageal Canc Inst, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
[3] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Hematol, Guangzhou 510180, Guangdong, Peoples R China
关键词
Angiogenesis; And-tumor activity; Multi-tyrosine kinases inhibitor; PBA2; VEGFR2; SMALL-MOLECULE INHIBITORS; GROWTH-FACTOR; IN-VITRO; CHEMOTHERAPEUTIC-AGENTS; CANCER; THERAPY; IDENTIFICATION; ACTIVATION; MECHANISMS; KINASES;
D O I
10.1016/j.bcp.2018.01.051
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
VEGFR2 (vascular endothelial growth factor receptor 2) is the main trigger of VEGF-mediated angiogenic signal and targeting VEGFR2 pathway to inhibit tumor angiogenesis represents a promising strategy for cancer therapy. We elucidated that a novel compound, PBA2 exhibited potent anti-tumor effects both in vitro and in vivo with limited toxicity. ELISA assay revealed that PBA2 had a strong suppressive activity against VEGFR2 related to angiogenesis. Furthermore, PBA2 considerably disrupted tube formation of endothelial cells in vitro and systemic administration of PBA2 exerted decreased tumor angiogenesis in vivo. Functional tests demonstrated that PBA2 concentration-dependently impeded the migration and proliferation of endothelial cells. PBA2 had no effects on the expression level of VEGF both in the detected cancer cells and endothelial cells. VEGFR2 and its downstream Akt and Erk pathways were blocked by PBA2 in a concentration-dependent manner both in vitro and in vivo. Overall, we first demonstrated that PBA2, targeting VEGFR2 related to angiogenesis, presented remarkable antiangiogenic and anti-tumor activities through attenuating VEGFR2 mediated pathway in vitro and in vivo with limited toxicity. These observations posed that PBA2 could be a potential drug candidate for developing antiangiogenic tyrosine kinase inhibitor in cancer therapy.
引用
收藏
页码:131 / 140
页数:10
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