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

作　　者：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 

机构地区：[1]Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu,221004,China [2]Department of Pharmacy,Affiliated Lianyungang Hospital of Xuzhou Medical University,Lianyungang,Jiangsu,222061,China [3]Department of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China [4]New Drug Screening Center,Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing,210009,China [5]School of Life Sciences,University of Essex,Essex CO43SQ,United Kingdom [6]Department of Urology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China [7]Department of Pharmacy,Affiliated Hospital of Jiangnan University,Wuxi,Jiangsu,214000,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第1期52-68,共17页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:81973377,81903689,82073906 and 82273987);the Key Natural Science Foundation of Jiangsu Higher Education Institutions of China(Grant Nos.:19KJB350006 and 19KJA460008);Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the initializing Fund of Xuzhou Medical University(Grant No.:D2018011);Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX21-2733 and KYCX22-2966).

摘　　要：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 dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(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 Yes-associated protein(YAP1)-TEA domain transcription factor(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.

关 键 词：METFORMIN Benign prostatic hyperplasia Sex steroid hormones homeostasis PROLIFERATION DHT YAP1-TEAD4 heterodimer 

分 类 号：R697.32[医药卫生—泌尿科学]