Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferationOA北大核心
Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation
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.How-ever,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 rela-tionship 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 over-expression 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.
Tingting Yang;Junjie Liu;Tao Wang;Xueyan Zhou;Sitong Qian;Jinfang Song;Yi Xu;Qian Lu;Xiaoxing Yin;Jiayu Yuan;Yuting Peng;Jiale Pang;Zhen Qiu;Shangxiu Chen;Yuhan Huang;Zhenzhou Jiang;Yilin Fan
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu,221004,ChinaDepartment of Urology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,ChinaDepartment of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu,221004,China||Department of Pharmacy,Affiliated Hospital of Jiangnan University,Wuxi,Jiangsu,214000,ChinaDepartment of Pharmacy,Affiliated Lianyungang Hospital of Xuzhou Medical University,Lianyungang,Jiangsu,222061,ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu,221004,China||Department of Pharmacy,Affiliated Lianyungang Hospital of Xuzhou Medical University,Lianyungang,Jiangsu,222061,ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu,221004,China||Department of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,ChinaNew Drug Screening Center,Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing,210009,ChinaSchool of Life Sciences,University of Essex,Essex CO4 3SQ,United Kingdom
MetforminBenign prostatic hyperplasiaSex steroid hormones homeostasisProliferationDHTYAP1-TEAD4 heterodimer
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The work was 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),and Post-graduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX21-2733 and KYCX22-2966).
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