Related Experiment Video

Updated: Jul 11, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

13.4K

The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel

Bisheng Cheng1, Lingfeng Li1, Yongxin Wu1

  • 1Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

Cell & Bioscience
|November 16, 2023
PubMed
Abstract

Insights

Ribonucleotide reductase subunit M2 (RRM2) drives docetaxel resistance in prostate cancer by stabilizing ANXA1 and activating the PI3K/AKT pathway. Targeting RRM2 or ANXA1 may overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate cancer is a significant cause of cancer deaths in men globally.
  • Docetaxel chemotherapy improves survival in castration-resistant prostate cancer (CRPC).
  • Drug resistance to docetaxel presents a major clinical challenge in CRPC treatment.

Purpose of the Study:

  • To investigate the role of Ribonucleotide reductase subunit M2 (RRM2) in docetaxel resistance in prostate cancer.
  • To explore the relationship between RRM2, ANXA1 expression, and the PI3K/AKT pathway in mediating resistance.
  • To evaluate the efficacy of targeting RRM2 and combination therapy for overcoming docetaxel resistance.

Main Methods:

  • Assessed RRM2 and ANXA1 expression in prostate cancer cell lines and xenografts.
  • Performed RRM2 knockdown and ANXA1 overexpression studies.
  • Investigated the impact of PI3K/AKT pathway inhibition.
  • Evaluated the synergistic effect of COH29 and docetaxel combination treatment.

Main Results:

  • Elevated RRM2 expression correlated with increased docetaxel resistance.
  • RRM2 knockdown sensitized prostate cancer cells to docetaxel.
  • RRM2 stabilizes ANXA1, activating the PI3K/AKT pathway and promoting resistance.
  • Combination treatment with COH29 and docetaxel showed synergistic effects.

Conclusions:

  • RRM2 promotes docetaxel resistance in prostate cancer via ANXA1 stabilization and PI3K/AKT pathway activation.
  • Targeting RRM2 or ANXA1 presents a potential therapeutic strategy.
  • Combination therapy with COH29 and docetaxel enhances treatment efficacy.
Keywords:
ChemotherapyDocetaxelOncologyProstate cancerRRM2

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