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

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

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  • 国家科技期刊平台
  • NETL
  • NSTL
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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.

MetforminBenign prostatic hyperplasiaSex steroid hormones homeostasisProliferationDHTYAP1-TEAD4 heterodimer

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

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Jiangsu 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,China

Department of Pharmacy,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China

New Drug Screening Center,Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical University,Nanjing,210009,China

School of Life Sciences,University of Essex,Essex CO4 3SQ,United Kingdom

Department of Urology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu,221006,China

Department of Pharmacy,Affiliated Hospital of Jiangnan University,Wuxi,Jiangsu,214000,China

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国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金Key Natural Science Foundation of Jiangsu Higher Education Institutions of ChinaKey Natural Science Foundation of Jiangsu Higher Education Institutions of China江苏高校优势学科建设工程项目initializing Fund of Xuzhou Medical UniversityPostgraduate Research Practice Innovation Program of Jiangsu ProvincePostgraduate Research Practice Innovation Program of Jiangsu Province

8197337781903689820739068227398719KJB35000619KJA460008D2018011KYCX21-2733KYCX22-2966

2024

10.1016/j.jpha.2023.08.012

药物分析学报(英文)
西安交通大学

药物分析学报(英文)

影响因子：0.244
ISSN：2095-1779
年,卷(期)：2024.14(1)
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