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Article Abstract
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.
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| http://dx.doi.org/10.1002/pros.21187 | DOI Listing |
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