RNAi-Mediated Gene Silencing of Vascular Endothelial Growth Factor Inhibits Growth of Colorectal Cancer

Abstract

Vascular endothelial growth factor (VEGF) is overexpressed in colorectal cancer (CRCs) cells and plays a critical role in angiopoiesis and cell proliferation, making it a potential target for cancer therapy. We developed a system that blocks VEGF in the human colorectal cancer cell line, HCT116, using RNA interference. By transfecting CRCs with the small interfering RNA (siRNA) that targets human VEGF, we were able to establish a stable clones in which VEGF expression was significantly downregulated (p < 0.01). This resulted in the decreased proliferation of HCT116 cells in vitro and suppressed the size of subcutaneous (s.c.) tumors and the microvessel density in an HCT116 s.c. nude mouse xenograft model in vivo (p < 0.01). These results suggest that a strategy based on siRNA targeting of VEGF may build the foundation to the clinical management of CRC.