Abstract

Arsenic trioxide (As₂O₃) has been used in the clinic for the treatment of acute promyelocytic 1eukemia 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-1α, Dll4 and Notch-1 in vivo. Moreover, As₂O₃ also inhibited the expression of HIF-1α, 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

Keywords: Angiogenesis, arsenic trioxide, Dll4, HIF-1α, lung cancer, Notch-1, VEGF, VEGFR-2.

Graphical Abstract