The novel VEGF receptor 2 inhibitor YLL545 inhibits angiogenesis and growth in breast cancer
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Jianbo Zhang1, Chen Liu1, Wen Shi2, Lingling Yang3, Quansheng Zhang4, Jianlin Cui2, Yangwu Fang2, Yuhao Li3, Guosheng Ren1, Shuang Yang2,* and Rong Xiang1,*
1 Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2 Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, China
3 School of Food and Bioengineering, Xihua University, Sichuan, China
4 Tianjin Key Laboratory of Organ Transplantation, Tianjin First Center Hospital, Tianjin, China
* These authors share senior co-authorship
Shuang Yang, email:
Rong Xiang, email:
Keywords: VEGFR2 inhibitor, angiogenesis, breast cancer, tumor gowth
Received: December 21, 2015 Accepted: April 16, 2016 Published: May 17, 2016
Their antiangiogenic effects make vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors useful for cancer treatment. However, most of these drugs have unexpected adverse side effects. Here, we show that the novel VEGFR2 inhibitor YLL545 suppressed tumor angiogenesis and growth in triple-negative breast cancer without adverse effects. YLL545 treatment also markedly inhibited proliferation, migration, invasion, and tube formation by human umbilical vascular endothelial cells (HUVECs) in vitro. These effects of YLL545 were equal to or greater than those seen with sorafenib. In addition, YLL545 inhibited VEGF-induced phosphorylation of VEGFR2 and activation of downstream signaling regulators, such as phospho-STAT3 and phospho-ERK1/2, in HUVECs. Embryonic angiogenesis assays in zebrafish and Matrigel plug assays in mice demonstrated that YLL545 inhibits angiogenesis in vivo. YLL545 also inhibited proliferation and induced apoptosis in MDA-MB-231 breast cancer cells both in vitro and in vivo, and 50 mg/kg/d YLL545 inhibited human tumor xenograft growth by more than 50% in BALB/c nude mice. These observations suggest YLL545 is a potentially useful anticancer drug candidate.
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