Synergistic effects of 7-O-geranylquercetin and siRNAs on the treatment of human breast cancer

Abstract

Aims: To investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer.

Main methods: Xenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice was measured by flow cytometer and living imaging sysytem, respectively. Cell viability was detected using CCK-8 assay. Cell apoptosis was determined by Hoechst33342 staining and AV-PI staining. Tumors bearing mice were administered with GQ by gavage, and/or with liposome CDO14 mediated siRNAs via tail intravenous injection. Expression levels of proteins and cytokines were detected by western blot and ELISA, respectively.

Key findings: Liposome CDO14 could deliver siRNA to tumor effectively. Combination of GQ and siSuvi promoted the antiproliferation and pro-apoptosis effects of GQ or siSuvi to MCF-7 cells, and reduced the level of survivin and raised the level of caspase-7 in cells. GQ combining with siSuvi inhibited the growth of tumor, down-regulated the expression of survivin and up-regulated the expression of caspase-7 in tumor tissue. Similarly, GQ combining with siIL-10 inhibited the growth of tumor, decreased the level of IL-10 and increased the level of TNF-α. These results revealed that GQ enhanced the pro-apoptosis effect of siSuvi on tumor cells and the modulating effect of siIL-10 on tumor microenvironment.

Significances: Synergistic anti-tumor effect of GQ and siRNAs against breast cancer proved that chemical drugs combining with siRNAs is a promising antitumor strategy.

Keywords: 7-O-geranylquercetin; Breast cancer; Interleukin-10; Survivin; siRNA.