siRNA-mediated knockdown of VEGF-A, VEGF-C and VEGFR-3 suppresses the growth and metastasis of mouse bladder carcinoma in vivo.

The growth of solid tumors is highly dependent on the formation of new blood and/or lymph vessels. Furthermore, metastases often disperse via newly formed blood or lymphatic vessels within the tumor, particularly in the case of epithelium-derived tumors. Since vascular endothelial growth factor (VEGF) signaling plays a vital role in angiogenesis and lymphangiogenesis, we used the small interfering RNA (siRNA) approach to selectively down-regulate VEGF-A, VEGF-C or VEGF receptor 3 (VEGFR-3) expression in bladder transitional carcinoma cells derived from T739 mice in an attempt to suppress tumor growth and metastasis in vivo. The synthetic siRNA was introduced into the tumor tissues by in vivo electroporation. The knockdown of VEGF-A, VEGF-C and VEGFR-3 expression significantly delayed tumor growth and reduced tumor metastasis compared to the negative controls. Thus, electroporation-mediated siRNA delivery to block the VEGF signaling pathway may provide a novel approach for the treatment or prevention of solid tumor growth and metastasis.