Combination therapy with VEGFR2 and EGFR siRNA enhances the antitumor effect of cisplatin in non-small cell lung cancer xenografts

Abstract

RNA targeting the murine vascular endothelial growth factor receptor 2 (VEGFR2) gene was designed and validated for efficient and robust silencing invitro and was delivered by polyethylenimines (PEI) invivo to investigate the antitumor effect on non-small cell lung cancer (NSCLC) xenografts. The following dosage regimens were tested for their tumor inhibitory effect invivo: VEGFR2 siRNA, epidermal growth factor receptor (EGFR) siRNA, VEGFR2 siRNA+EGFR siRNA, cisplatin alone and VEGFR2 siRNA+ EGFR siRNA+cisplatin. Targeted silencing of both VEGFR2 and EGFR expression by siRNA, combined with low-dose cisplatin, was found to effectively inhibit tumor growth and extend the survival time of mice bearing the NSCLC xenografts. These results suggest that combination therapy using siRNAs and chemotherapy agents might offer a novel strategy for cancer treatment in the future.