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YAP1-TEAD4
Journal of Pharmaceutical Analysis · 2023 · IF 8.8

Metformin: A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

Tingting Yang,Jiayu Yuan,Yuting Peng,Jiale Pang,Zhen Qiu,Shangxiu Chen,Yuhan Huang,Zhenzhou Jiang,Yilin Fan,Junjie Liu,Tao Wang,Xueyan Zhou,Sitong Qian,Jinfang Song,Yi Xu,Qian Lu,Xiaoxing Yin

The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated DHT had a significant positive relationship with the clinical characteristics of BPH patients. Activation of AMPK by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated YAP1-TEAD4 heterodimers. Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

研究领域: 泌尿学 · 内分泌学 · 药理学 · 细胞生物学
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