2. Academic Validation
  3. Regression of Castration-Resistant Prostate Cancer by a Novel Compound HG122

Regression of Castration-Resistant Prostate Cancer by a Novel Compound HG122

  • Front Oncol. 2021 Jun 3;11:650919. doi: 10.3389/fonc.2021.650919.
Xiaonan Cong 1,  Yundong He 1,  Haigang Wu 1,  Dingxiang Wang 1,  Yongrui Liu 1,  Ting Shao 1,  Mingyao Liu 1,  Zhengfang Yi 1,  Jianghua Zheng 2,  Shihong Peng 1,  Tao Ding 3 4
Affiliations

Affiliations

  • 1 East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • 2 Department of Laboratory Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
  • 3 Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China.
  • 4 Southern Medical University Affiliated Fengxian Hospital, Shanghai, China.
PMID: 34150618 DOI: 10.3389/fonc.2021.650919
Abstract

Prostate Cancer (PCa) is a common aggressive disease worldwide which usually progresses into incurable castration-resistant prostate Cancer (CRPC) in most cases after 18-24 months treatment. Androgen Receptor (AR) has been considered as a crucial factor involved in CRPC and the study of AR as a potential therapeutic target in CRPC may be helpful in disease control and life-cycle management. In this study, we identified a potent small molecule compound, HG122, that suppressed CRPC cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous and orthotopic tumor model. In addition, HG122 reduced the mRNA expression of PSA and TMPRSS2 which are target genes of AR, resulting in cell growth inhibition and metastasis suppression of CRPC, without affecting the expression of AR mRNA level. Mechanically, HG122 promoted AR protein degradation through the Proteasome pathway impairing the AR signaling pathway. In conclusion, HG122 overcomes enzalutamide (ENZ) resistance in CRPC both in vitro and in vivo, thus suggesting HG122 is a potential candidate for the clinical prevention and treatment of CRPC.

Keywords

HG122; androgen receptor; cancer treatment; castration-resistant prostate cancer; molecular compound.

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