Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in

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Updated: Feb 25, 2026

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

14.1K

Yun-Fei Li1, Hui-Hua Ji1, Zheng-Long Zhang1

  • 1Department of Urology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.

Oncology Letters
|August 10, 2017
PubMed

Insights

Multidrug resistance protein 4 (MRP4) overexpression causes docetaxel (DTX) resistance in prostate cancer. Anti-androgen therapy can inhibit MRP4, resensitizing tumors to DTX chemotherapy and improving treatment outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Docetaxel (DTX) improves survival in castration-resistant prostate cancer (CRPC), but resistance limits efficacy.
  • Multidrug resistance protein 4 (MRP4) is implicated in chemotherapy resistance.
  • Targeting resistance mechanisms is crucial for effective CRPC treatment.

Purpose of the Study:

  • Investigate MRP4 expression in DTX-resistant prostate cancer cells.
  • Determine if anti-androgen treatment can inhibit MRP4 and overcome DTX resistance.

Main Methods:

  • Established DTX-resistant C4-2/D cells from sensitive C4-2/S cells.
  • Assessed MRP4 gene and protein expression via RT-PCR and Western blotting.
  • Evaluated DTX intracellular/extracellular concentrations using HPLC and cytotoxicity assays.

Main Results:

  • MRP4 was significantly overexpressed in DTX-resistant C4-2/D cells compared to C4-2/S cells.
  • Androgen dihydrotestosterone increased MRP4 expression; anti-androgen bicalutamide (BKL) blocked this effect.
  • BKL treatment downregulated MRP4, increased intracellular DTX, and resensitized C4-2/D cells to DTX.

Conclusions:

  • MRP4 overexpression mediates acquired DTX resistance in prostate cancer.
  • Targeting MRP4 with anti-androgen therapy may reverse DTX resistance, offering a potential strategy to re-sensitize prostate cancer cells to chemotherapy.
Keywords:
androgenbicalutamidecastration-resistant prostate cancerdocetaxelmultidrug resistance protein 4

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