Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2-mediated signaling pathways in lung cancer

作者：Li, Fajiu; Huang, Jie; Ji, Dongyuan; Meng, Qinghua; Wang, Chuanhai; Chen, Shi; Wang, Xiaojiang; Zhu, Zhiyang; Jiang, Cheng; Shi, Yi; Liu, Shuang; Li, Chenghong^*

来源：Oncology Letters, 2017, 14(1): 89-96.

DOI：10.3892/ol.2017.6103

• azithromycin
• tumor angiogenesis
• lung cancer
• vascular endothelial growth factor/vascular endothelial growth factor receptor 2 signaling
• focal adhesion
• phosphoinositide 3-kinase/Akt

Tumor angiogenesis is essential during lung cancer development and targeting angiogenesis may possess a potential therapeutic value. The present study demonstrates that azithromycin, a Food and Drug Administration-approved antibiotic drug, is a novel tumor angiogenesis inhibitor. Azithromycin inhibits capillary network formation of human lung tumor associated-endothelial cells (HLT-ECs) in vitro and in vivo. It significantly inhibits HLT-EC adhesion and vascular endothelial growth factor (VEGF)-induced proliferation of HLT-ECs in a dose-dependent manner without affecting migration. In addition, azithromycin induces apoptosis of HLT-ECs even in the presence of VEGF. Notably, azithromycin inhibits proliferation and induces apoptosis in multiple lung cancer cell lines to a significantly reduced extent compared with in HLT-ECs, suggesting that HLT-ECs are more susceptible to azithromycin treatment. In a lung tumor xenograft model, azithromycin significantly inhibits tumor growth and its anti-tumor activities are achieved by suppressing angiogenesis. Notably, the inhibitory effects of azithromycin on angiogenesis are associated with its ability to suppress VEGF-induced activation of VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), focal adhesion kinase, and disruption of focal adhesion assembly and actin stress fiber formation in HLT-ECs. The present study identifies that azithromycin targets VEGFR2-mediated focal adhesion and PI3K/Akt signaling pathways in HLT-ECs, leading to the suppression of angiogenesis and lung tumor growth.

• 出版日期2017-7
• 单位江汉大学