An In Vitro Model for Preclinical Testing of Endocrine Therapy Combinations for Prostate Cancer

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 5 alpha-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. Prostate 70: 1524-1532, 2010. (C) 2010 Wiley-Liss, Inc.