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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Anti-Androgen Abiraterone Acetate Improves the Therapeutic Efficacy of Statins on Castration-Resistant Prostate

Dannah R Miller1, Matthew A Ingersoll1, Yu-Wei Chou1,2

  • 1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

Journal of Oncology Research and Therapy
|July 23, 2019
PubMed

Insights

Statins like simvastatin inhibit castration-resistant prostate cancer (CR PCa) growth by targeting androgen synthesis. Combining statins with abiraterone acetate enhances anti-androgen therapy for CR PCa.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Castration-resistant prostate cancer (CR PCa) presents limited treatment options.
  • Some CR PCa tumors sustain growth via intracrine androgen receptor (AR) activation through de novo androgen synthesis.
  • Targeting androgen biosynthesis is a potential therapeutic strategy for CR PCa.

Purpose of the Study:

  • To investigate the efficacy of androgen biosynthesis inhibitors, specifically statins (simvastatin, atorvastatin) and ketoconazole, against CR PCa cells.
  • To evaluate the synergistic effects of statins in combination with the anti-androgen abiraterone acetate.

Main Methods:

  • In vitro assessment of growth, migration, and colony formation inhibition in LNCaP C-81 cells (a model for de novo androgen synthesis in CR PCa).
  • Evaluation of combination treatments involving statins and abiraterone acetate.

Main Results:

  • Simvastatin, atorvastatin, and ketoconazole directly inhibited growth, migration, and colony formation of LNCaP C-81 cells.
  • Simvastatin demonstrated the most potent inhibitory effect.
  • Combination therapy with statins and abiraterone acetate showed enhanced growth suppression compared to individual treatments.

Conclusions:

  • Statins are effective inhibitors of androgen biosynthesis in CR PCa cells.
  • Statins can potentiate the effects of abiraterone acetate, suggesting a role in combination therapy to improve treatment outcomes for CR PCa.
Keywords:
Anti-AndrogensCastration-Resistant Prostate CancerCombination TreatmentsProstate CancerStatins

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