Trillin inhibits MAP3K11/NF-κB/COX-2 signaling pathways through upregulation of miR-145-5p in castration-resistant prostate cancer
Yanlong Wang,
Yulin Peng,
Wenjun Hao,
Chengjian He,
Xiang Gao,
Peng Liang,
Haolin Zhao,
Ying Wang,
Liang Wang,
Zhenlong Yu,
Zhiyu Liu
Affiliations
Yanlong Wang
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Yulin Peng
College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian 116044, China
Wenjun Hao
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Chengjian He
College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian 116044, China
Xiang Gao
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Peng Liang
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Haolin Zhao
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Ying Wang
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Liang Wang
Department of Urology, The Second Hospital of Dalian Medical University, Dalian 116023, China
Zhenlong Yu
College of Integrative Medicine, College of Pharmacy, Dalian Medical University, Dalian 116044, China; Corresponding author
Zhiyu Liu
Department of Urology, The Second Hospital of Dalian Medical University, Liaoning Provincial Key Laboratory of Urological Digital Precision Diagnosis and Treatment, Liaoning Engineering Research Center of Integrated Precision Diagnosis and Treatment Technology for Urological Cancer, Dalian Key Laboratory of Prostate Cancer Research, Dalian 116023, China; Corresponding author
Summary: Castration-resistant prostate cancer (CRPC) presents a significant challenge in treatment following androgen deprivation therapy. This study evaluates Trillin, a compound with antioxidant and anti-inflammatory properties, for its therapeutic potential against CRPC. Using DU145 and PC3 cell lines and a mouse xenograft model, we demonstrate that Trillin effectively inhibits CRPC cell viability, proliferation, migration, and invasion while promoting apoptosis and cell-cycle arrest. Mechanistic investigations reveal that Trillin disrupts NF-κB/COX-2 signaling by downregulating MAP3K11 and COX-2 and inhibiting the nuclear translocation of NF-κB subunits. Additionally, Trillin enhances the expression of miR-145-5p, further modulating pathways critical for CRPC progression. These findings suggest that Trillin may offer a promising alternative approach for targeting CRPC, highlighting its potential as a therapeutic agent to improve patient outcomes.
