Trillin-Mediated Inhibition of NF-κB/COX-2 Signaling Pathways through Upregulation of miR-145-5p Targeting MAP3K11 in Castration-Resistant Prostate Cancer

Author:

Wang Yanlong1,Peng Yulin2,Hao Wenjun1,Gao Xiang1,Liang Peng1,Zhao Haolin1,Wang Ying1,Wang Liang1,Yu Zhenlong2,Liu Zhiyu1

Affiliation:

1. Second Affiliated Hospital of Dalian Medical University

2. Dalian Medical University

Abstract

Abstract Purpose Prostate cancer remains a leading cause of cancer-related deaths among men worldwide, driving the need for innovative therapeutic avenues. Despite preliminary evidence supporting the anti-cancer potential of the natural compound Trillin, its effectiveness against castration-resistant prostate cancer (CRPC) has yet to be fully explored. Methods This study evaluated the anti-cancer efficacy of Trillin in CRPC cell lines DU145 and PC3 through a comprehensive set of in vitro and in vivo experiments. Assessments included cell proliferation, migration, invasion, apoptosis, and cell cycle analyses, alongside Western blot, qRT-PCR, confocal immunofluorescence, and dual luciferase assays to elucidate the molecular mechanisms underlying Trillin's action. Additionally, an in vivo CRPC xenograft model in NYG immunodeficient mice was used to assess therapeutic efficacy and toxicity. Results Trillin treatment significantly reduced CRPC cell viability, proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest at the G0/G1 phase. Mechanistically, Trillin downregulated key proteins involved in the NF-κB/COX-2 pathway, inhibited nuclear translocation of NF-κB subunits, and decreased COX-2 promoter activity. It also upregulated miR-145-5p, targeting MAP3K11, which is implicated in CRPC progression. In vivo, Trillin markedly suppressed tumor growth without observable toxicity, highlighting its potential as a therapeutic agent. Conclusion Our findings demonstrate that Trillin significantly inhibits the growth and metastatic capabilities of CRPC cells, both in vitro and in vivo, through induction of apoptosis, cell cycle arrest, and suppression of the NF-κB/COX-2 signaling pathway. By modulating miR-145-5p and targeting MAP3K11, Trillin presents a promising therapeutic strategy for CRPC, warranting further clinical investigation.

Publisher

Research Square Platform LLC

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