Combination gene therapy using VEGF-shRNA and fusion suicide gene yCDglyTK inhibits gastric carcinoma growth

Clinical trials of suicide gene therapy have achieved limited success, which suggests a need for improvement. Angiogenesis plays a crucial role in the progression of cancers, which is greatly regulated by vascular endothelial growth factor (VEGF).The current study was designed to evaluate the anti-tumor effects of VEGF siRNA in combination with fusion suicide gene yCDglyTK. Introduction of a VEGF-targeted small hairpin RNA (shVEGF) to CDTK/5-FC system could induce cell apoptosis more effectively and decrease micro vessel density in xenograft tissue, thus resulted in a significant tumor growth delay in SGC7901 xenografts. These findings for the first time suggest the potential of combination gene therapy using suicide gene therapy and anti-angiogenesis gene therapy.

► A triple-gene vector expressing VEGF-shRNA and fusion suicide gene yCDglyTK was constructed and delivered it into SGC7901 cells by calcium phosphate nanoparticles. ► The VEGF-targeted RNAi had a synergistic effect with suicide gene therapies. ► The combination gene therapy system could kill SGC7901 cells effectively in vitro and significantly suppress the tumor growth of SGC7901 xenografts in mice.