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Updated: May 9, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Testosterone boosts for treatment of castration resistant prostate cancer: an experimental implementation of
Paul Thelen1, Elmar Heinrich, Felix Bremmer
1Department of Urology, University Medical Center Göttingen, Göttingen, Germany.
Background:
The primary therapeutic target for non-organ-confined prostate cancer is the androgen receptor (AR). Main strategies to ablate AR function are androgen depletion and direct receptor blockade by AR antagonists. However, incurable castration resistant prostate cancer (CRPC) develops resistance mechanisms to cope with trace amounts of androgen including AR overexpression and mutation in the AR ligand binding domain.
Methods:
The CRPC cell model VCaP derivative of a prostate cancer bone metastasis was used in vitro and in nude mice in vivo to examine the effects of immediate testosterone boost on CRPC cells. In addition, a testosterone tolerant cell model was established by incremental acclimatization of VCaP cells to 1 nM testosterone. The effects of androgen withdrawal and testosterone boosts on gene expression were assessed by quantitative real-time polymerase chain reaction, ELISA, and Western blots. Tumor cell proliferation was evaluated with a BrdU test.
Results:
Testosterone boosts on CRPC VCaP cells eliminate tumor cells to a higher extent than androgen withdrawal in androgen tolerant cells. The pronounced decrease of tumor cell proliferation was accompanied by a marked downregulation of AR expression regarding full-length AR and splice variant AR V7.
Conclusions:
Acquiring castration resistance of prostate cancer cells by AR overexpression and amplification obviously sensitizes such cells to testosterone concentrations as low as physiological values. This introduces novel therapeutic means to treat CRPC with non-toxic measures and may find clinical implementation in intermittent androgen deprivation regimens.
Insights
Testosterone boosts effectively eliminate castration-resistant prostate cancer (CRPC) cells by downregulating androgen receptor (AR) expression. This finding offers new, non-toxic therapeutic strategies for CRPC treatment.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- The androgen receptor (AR) is the main target for non-organ-confined prostate cancer.
- Castration-resistant prostate cancer (CRPC) develops resistance to androgen depletion via AR overexpression or mutation.
- Current therapies include androgen depletion and AR antagonists, but resistance remains a challenge.
Purpose of the Study:
- To investigate the effects of immediate testosterone boosts on CRPC cells.
- To establish and study a testosterone-tolerant CRPC cell model.
- To assess the impact of androgen withdrawal and testosterone boosts on AR signaling and cell proliferation.
Main Methods:
- Utilized the VCaP CRPC cell line in vitro and in vivo (nude mice).
- Established a testosterone-tolerant cell model through incremental acclimatization.
- Assessed gene expression via qPCR, ELISA, and Western blots; evaluated proliferation using BrdU assay.
Main Results:
- Testosterone boosts were more effective in eliminating CRPC VCaP cells than androgen withdrawal in tolerant cells.
- A significant decrease in tumor cell proliferation was observed.
- Marked downregulation of both full-length AR and AR-V7 splice variant expression was noted.
Conclusions:
- AR overexpression and amplification in CRPC cells sensitize them to physiological testosterone levels.
- This suggests novel, non-toxic therapeutic approaches for CRPC.
- Findings may inform intermittent androgen deprivation regimens for clinical use.
