Blockade of VEGF-A suppresses tumor growth via inhibition of autocrine signaling through FAK and AKT

Abstract

Blockade of VEGF signaling using RNA interferences, a neutralizing antibody, an antagonizing soluble VEGF receptor, and a receptor tyrosine kinase inhibitor induced anti-tumor effects in human astrocytoma U251-MG and fibrosarcoma HT-1080 in vitro in a dose-dependent manner. Furthermore, blockade of VEGF-A using the doxycycline-inducible VEGF-A RNA interference system showed a significant antitumor effect in a murine HT-1080-xenograft model. Anti-tumor effect through the blockade of VEGF signaling was mediated by FAK and AKT pathway in vitro and in vivo. These results collectively indicate that VEGF-A and its receptors can act as key inducer of tumor growth as well as angiogenesis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.