Zoledronate suppresses VEGF-induced capillary tube formation and inhibits expression of interferon-induced transmembrane protein-1 in human umbilical vein endothelial cells

Abstract

Interferon-induced transmembrane protein 1 (IFITM1) is a member of the interferon-induced transmembrane protein family and has recently been identified as a novel protein participant in angiogenesis. Zoledronate (ZON), a nitrogen-containing bisphosphonate, is widely used in the treatment of osteoporosis and to prevent bone metastases of certain cancer types. However, the association between ZON and IFITM1 has remained elusive. The present study investigated the effect of ZON on the expression of IFITM1 during vascular endothelial growth factor (VEGF)-induced capillary tube formation in human umbilical vein endothelial cells. It was observed that cell proliferation and VEGF-induced tube formation were significantly inhibited by treatment with 10μM ZON. The expression of IFITM1 increased during VEGF-induced tube formation. However, the VEGF-induced increase in IFITM1 expression exhibited a dose- and time-dependent decrease with ZON treatment at the mRNA and protein level. Furthermore, matrix metalloproteinase-9 activation was markedly decreased by ZON treatment. These results suggest that induction of IFITM1 expression may be involved in the anti-angiogenic activity of ZON.