Metformin mitigates PLCε gene expression and modulates the Notch1/Hes and androgen receptor signaling pathways in castration-resistant prostate cancer xenograft models.

Abstract

The present study aimed to establish a mouse model of patient-derived castration-resistant prostate cancer (CRPC) xenograft tumors, and to evaluate the effects of various doses of metformin on phospholipase Cε (PLCε) expression and the neurogenic locus notch homolog protein 1 (Notch1)/hairy and enhancer of split 1 and androgen receptor (AR) signaling pathways via western blotting and reverse transcription-quantitative PCR. Additionally, phorbol 12-myristate 13-acetate was used to activate PLC, and Jagged1 was used as a Notch activator to verify whether metformin could suppress CRPC development via the PLCε/Notch1/AR pathways. The results confirmed that metformin may serve critical roles in CRPC by significantly inhibiting the occurrence, growth and proliferation of CRPC tumors by decreasing PLCε/Notch1 expression and AR nucleation.