Liposome-based co-delivery of 7-O-geranyl-quercetin and IGF-1R siRNA for the synergistic treatment of non-small cell lung cancer

Abstract The combination of siRNAs and chemical drugs for the treatment of tumors has received more and more attention. This study investigated the synergistic effect of 7-O-geranyl quercetin (GQ) and IGF-1R siRNA (siIGF-1R) co-delivered by a liposome on human non-small cell lung cancer (NSCLC). GQ was firstly loaded with cationic liposome CDO14 to form CDO14-GQ which then combined with siIGF-1R to form co-delivery liposome CDO14-GQ-siIGF-1R. CCk-8 assay indicated that CDO14-GQ-siIGF-1R enhanced the anti-proliferation effect of CDO14-GQ or CDO14-siIGF-1R in NCI–H460 and A549 cells, AO/EB and AV/PI staining assays showed that the co-delivery liposome increased the pro-apoptosis effect of CDO14-GQ or CDO14-siIGF-1R. The growth inhibition effect of CDO14-GQ-siIGF-1R on the xenograft of NCI–H460 and A549 cells in mice was much stronger than that of CDO14-GQ or CDO14-siIGF-1R. Western blot assay indicated that CDO14-GQ-siIGF-1R down-regulated the expression levels of siIGF-1R in cells and in tumor tissues, and its effect on the expression of apoptosis-related proteins Bcl-2 and Bax was stronger than that of CDO14-GQ or CDO14-siIGF-1R. These results demonstrated that co-delivery of GQ and siIGF-1R by liposome improved the antitumor effect of either of them. Our study highlight that siRNAs combined with chemotherapeutic drugs is a promising strategy for the treatment of NSCLC.