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An in vitro model for preclinical testing of endocrine therapy combinations for prostate cancer
Author(s) -
Pfeiffer Minja J.,
Mulders Peter F.,
Schalken Jack A.
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21187
Subject(s) - prostate cancer , bicalutamide , antiandrogen , androgen receptor , cancer research , viability assay , lncap , medicine , tmprss2 , prostate , cancer , oncology , endocrinology , cell , biology , biochemistry , disease , covid-19 , infectious disease (medical specialty)
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 5α‐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. © 2010 Wiley‐Liss, Inc.