Related Experiment Video

Updated: Aug 13, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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Immunoproteasome inhibition prevents progression of castration-resistant prostate cancer

Jun Li1, Nan Liu2, Hong Zhou2

  • 1Department of Urologic Oncology Surgery, Chongqing University Cancer Hospital, 400030, Chongqing, China. lijunmed@cqu.edu.cn.

British Journal of Cancer
|January 21, 2023
PubMed
Abstract

Insights

Immunoproteasome inhibition, a novel immunotherapy, effectively suppresses castration-resistant prostate cancer (CRPC) progression. This approach targets key inflammatory and signaling pathways, offering a promising therapeutic strategy for CRPC treatment.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Castration-resistant prostate cancer (CRPC) is a hormone-refractory malignancy.
  • Novel therapeutic strategies are crucial for managing CRPC progression.

Purpose of the Study:

  • To investigate the efficacy of immunoproteasome inhibition as a novel immunotherapy for CRPC.
  • To elucidate the underlying mechanisms by which immunoproteasome inhibition affects CRPC progression.

Main Methods:

  • Utilized gene knockout and the epoxyketone inhibitor ONX 0914 to target the immunoproteasome subunit LMP7.
  • Employed a mouse CRPC tumor graft model and in vitro human CRPC cell lines.
  • Analyzed inflammatory responses, tumor progression, angiogenesis, epithelial-mesenchymal transition, and apoptosis.

Main Results:

  • Selective LMP7 inhibition with ONX 0914 suppressed the Th17 inflammatory response and CRPC progression.
  • Immunoproteasome inhibition reduced IL-17-induced angiogenesis and epithelial-mesenchymal transition by inactivating COX-2/VEGF-A and β-catenin/Snail signaling.
  • Immunoproteasome inhibition induced CRPC cell apoptosis via unfolded protein response activation.

Conclusions:

  • The immunoproteasome plays a critical role in CRPC progression.
  • Immunoproteasome inhibition is a promising therapeutic approach for suppressing CRPC progression.

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