Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation.

Arsenic trioxide (AsO) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of AsO on lung cancer and explored its possible mechanism. It was observed that AsO significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis . The inhibitory effect of AsO on cell proliferation was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that AsO inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-β, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by AsO. These findings suggested that anti-angiogenesis may be an underlying mechanism of AsO anticancer activity in lung cancer.