Arsenic Trioxide Exerts Anti-lung Cancer Activity by Inhibiting Angiogenesis

作者：Yang, Meng-Hang; Zang, Yuan-Sheng; Huang, Hai; Chen, Kun; Li, Bing^*; Sun, Guang-Yuan; Zhao, Xue-Wei

来源：Current Cancer Drug Targets, 2014, 14(6): 557-566.

DOI：10.2174/1568009614666140725090000

• Angiogenesis
• arsenic trioxide
• Dll4
• HIF-1 alpha
• lung cancer
• Notch-1
• VEGF
• VEGFR-2

Arsenic trioxide (As2O3) has been used in the clinic for the treatment of acute promyelocytic leukemia and some solid tumors. However, its effectiveness against lung cancer has not been well demonstrated, and the underlying mechanism(s) of action remain unclear. In the present study, we found that As2O3 significantly inhibited the growth of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) xenograft tumors. It was observed to have antiangiogenic effects in xenograft models and matrigel pellets. It also significantly inhibited the expression of VEGF-A, VEGFR-2, HIF-1 alpha, Dll4 and Notch-1 in vivo. Moreover, As2O3 also inhibited the expression of HIF-1 alpha, VEGFR-2, Dll4, and Notch-1 in lung cancer cell lines and human umbilical vein endothelial cells. These findings suggest that As2O3 has significant anti-lung cancer activity, which may occur as a result of the antiangiogenic effects caused by the downregulation of the VEGF and Dll4-Notch signaling pathways.

• 出版日期2014
• 单位中国人民解放军第二军医大学; 天津市中医药研究院附属医院