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Updated: Mar 2, 2026

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

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Niclosamide and Bicalutamide Combination Treatment Overcomes Enzalutamide- and Bicalutamide-Resistant Prostate Cancer

Chengfei Liu1, Cameron M Armstrong1, Wei Lou1

  • 1Department of Urology, University of California Davis, California.

Molecular Cancer Therapeutics
|May 14, 2017
PubMed

Insights

Androgen receptor (AR) variants, especially AR-V7, drive resistance to bicalutamide in prostate cancer. Targeting AR variants with niclosamide resensitizes cells to bicalutamide and inhibits tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Androgen receptor (AR) activation and splice variants are implicated in advanced prostate cancer.
  • AR and its variants' roles in resistance to androgen deprivation therapy (ADT) and bicalutamide are not fully understood.

Purpose of the Study:

  • To investigate the role of AR variants in bicalutamide resistance.
  • To evaluate the efficacy of targeting AR variants with niclosamide in combination with bicalutamide.

Main Methods:

  • Developed bicalutamide-resistant LNCaP cells (LNCaP-BicR).
  • Assessed AR variant expression (mRNA and protein) in resistant cells.
  • Utilized AR-V7 knockdown and exogenous expression studies.
  • Investigated the effects of niclosamide and bicalutamide combination treatment on resistant cells and tumors.

Main Results:

  • Bicalutamide-resistant cells showed significantly increased AR variant levels, particularly AR-V7.
  • Exogenous AR-V7 expression conferred bicalutamide resistance.
  • AR-V7 knockdown reversed resistance in multiple resistant cell lines.
  • Niclosamide enhanced bicalutamide efficacy, suppressed AR signaling, induced apoptosis, and inhibited tumor growth.

Conclusions:

  • AR variants, especially AR-V7, are key drivers of bicalutamide resistance in prostate cancer.
  • Targeting AR-V7 with niclosamide can overcome bicalutamide resistance.
  • Combination therapy with niclosamide and bicalutamide shows potential for treating advanced prostate cancer, including enzalutamide-resistant cases.

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