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Updated: Jun 10, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
An in vitro model for preclinical testing of endocrine therapy combinations for prostate cancer
Minja J Pfeiffer1, Peter F Mulders, Jack A Schalken
1Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Background:
Even though patients with prostate cancer commonly respond to endocrine treatment, in most cases the disease progresses to castration resistant prostate cancer (CRPC). Our objective was to generate a novel cell line model representing the endocrine treatment naive prostate cancer for testing treatments that target the androgen receptor (AR) and androgen metabolism.
Methods:
After culturing DuCaP cells 20 passages with additional 1 nM R1881, DuCaP-N(aive) cell line was developed and validated for testing endocrine therapy combinations. Cell viability, apoptosis and cell cycle distribution were assessed in DuCaP and DuCaP-N when interfering with the hormonal content.
Results:
Addition of 1 nM R1881 to DuCaP reduces cell viability and induces cell cycle inhibition and apoptosis. Eventually, an androgen accustomed DuCaP-N cell line developed. An antiandrogen (bicalutamide), a histone deacetylase (HDAC) inhibitor (trichostatin A) and a 5alpha-reductase (SRD5A) inhibitor (finasteride) reduce cell viability, and their combinations give a synergistic response in inducing apoptosis.
Conclusions:
The TMPRSS2-ERG expressing DuCaP-N cell line represents human prostate cancer prior to endocrine treatment, and its parental DuCaP cell line is a model for CRPC. These cell lines can be used for preclinical evaluation of compounds that target the androgenic pathway.
Insights
A new prostate cancer cell line, DuCaP-N, models endocrine-naive disease for testing androgen receptor (AR) targeted therapies. This model aids in evaluating new treatments for prostate cancer before it becomes castration-resistant prostate cancer (CRPC).
Area of Science:
- Oncology
- Cell Biology
- Endocrinology
Background:
- Prostate cancer often progresses to castration-resistant prostate cancer (CRPC) despite initial response to endocrine treatment.
- Novel cell line models are crucial for studying early-stage prostate cancer and developing targeted therapies.
- The androgen receptor (AR) and androgen metabolism are key targets in prostate cancer treatment.
Purpose of the Study:
- To develop a novel cell line model for endocrine treatment-naive prostate cancer.
- To validate the DuCaP-N cell line for testing treatments targeting the androgen receptor (AR) and androgen metabolism.
- To provide a preclinical model for evaluating novel therapeutic strategies against prostate cancer.
Main Methods:
- The DuCaP cell line was cultured with R1881 to establish the DuCaP-N cell line.
- Cell viability, apoptosis, and cell cycle distribution were assessed in DuCaP and DuCaP-N cells.
- The effects of antiandrogen, HDAC inhibitor, and SRD5A inhibitor were evaluated individually and in combination.
Main Results:
- R1881 treatment reduced viability and induced apoptosis and cell cycle inhibition in DuCaP cells, leading to the development of the androgen-accustomed DuCaP-N cell line.
- Antiandrogen (bicalutamide), HDAC inhibitor (trichostatin A), and SRD5A inhibitor (finasteride) all reduced cell viability.
- Combinations of these inhibitors showed synergistic effects in inducing apoptosis, highlighting potential therapeutic strategies.
Conclusions:
- The DuCaP-N cell line, expressing TMPRSS2-ERG, effectively models human prostate cancer prior to endocrine treatment.
- The parental DuCaP cell line serves as a model for castration-resistant prostate cancer (CRPC).
- These cell lines are valuable tools for the preclinical evaluation of compounds targeting the androgenic pathway in prostate cancer.
