Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway

Abstract

The aim of present study was to examine whether metformin in association with quercetin has any synergistically anti-tumor effects on prostate cancer. Our findings showed that metformin in combination with quercetin synergistically inhibited the growth, migration and invasion of both PC-3 and LNCaP cells. Co-treatment of these two agents induced more apoptosis than single agent treatment. The co-treatment-induced apoptosis was caspase-dependent and accompanied by the down-regulation of Bcl-2 family members. Our data also indicated that co-treatment of metformin and quercetin strongly inhibited the VEGF/Akt/PI3K pathway. Moreover, these two agents acted synergistically to repress the growth of human prostate cancer cell xenograft in vivo in nude mice. In conclusion, our findings indicate that the combination therapy of metformin and quercetin exerted synergistic antitumor effects in prostate cancers via inhibition of VEGF/Akt/PI3K pathway. Thus, combination treatment of metformin and quercetin would be a promising therapeutic strategy for prostate cancer patients.

Keywords: Apoptosis; Metformin; Prostate cancer; Quercetin; VEGF/Akt/PI3K.