Lentivirus-mediated RNAi knockdown of VEGFA in RKO colorectal cancer cells decreases tumor formation and growth in vitro and in vivo.

Vascular endothelial growth factors (VEGF) play important roles in angiogenesis, vasculogenesis and endothelial cell growth. In endothelial cancers, secreted VEGF proteins induce endothelial cell proliferation, promote cell migration, inhibit apoptosis and induce blood vessel permeabilization. VEGFA is frequently overexpressed in human colorectal cancers (CRC) and its expression correlates with tumor progression and invasiveness. In this study we examine the effect of knocking down VEGFA expression by infecting RKO colorectal cancer cells with lentiviral particles containing VEGFA-targeting RNAi constructs. We found that suppressing VEGFA dramatically decreased RKO cell proliferation, colony formation, invasion, migration and tumor growth. Furthermore, VEGFA knock-down reduced MAPK pathway signaling and Smac/DIABLO expression. These results suggest that lentivirus-mediated RNAi knock-down of VEGFA could be an effective therapy for the treatment of CRC.