Inhibiting tumor growth of colorectal cancer by blocking the expression of vascular endothelial growth factor receptor 3 using interference vector-based RNA interference

Abstract

Many reports show that vascular endothelial growth factor receptor 3 (VEGFR3) plays an essential role in tumor metastasis and is a promising target for cancer therapy. The present study was designed to determine the role of VEGFR3 in tumor growth using RNA interference (RNAi) technology. Three small interfering RNA (siRNA) sequences for the VEGFR3 gene were cloned into expression plasmids (pSUPER) and transfected into human colorectal carcinoma (CRC) LoVo cells. Stable transfection of these plasmids decreased VEGFR3 protein expression, leading to the potent suppression of tumor cell proliferation and lymphangiogenesis in vitro. Furthermore, we selected the most effective silenced expressor vector and injected it and pSUPER vector into a tumor xenograft model in nude mice. The tumor growth of LoVo cells expressing VEGFR3 siRNA were significantly inhibited compared with cells transfected with control vector alone. Immunohistochemical analyses of tumor sections revealed a decreased vessel density and decreased VEGFR3 expression in animals when siRNA against VEGFR3 was expressed. These results showed that RNAi of VEGFR3 is an effective tool to reduce lymphangiogenesis in CRC.