Dual-Targeting of AR and Akt Pathways by Berberine in Castration- Resistant Prostate Cancer.

摘要

In this grant period, we completed testing the efficacy of berberine in intact Pten-null mice. In addition to inhibiting tumor development, berberine suppresses AR and AKT pathways simultaneously. We found BEZ235 treatment was not effective in this model of prostate cancer, despite its potent inhibition on AKT activation. This is possibly due to a compensatory induction of AR-mediated signaling. We further demonstrated that berberine inhibits the development of castration-resistant prostate cancer in castrated Pten-null mice. In addition, we provided initial evidence of berberine s efficacy against castrationresistance prostate cancer driven by a constitutively active AR splice variant.