Open AccessAssessment of STAT5 as a potential therapy target in enzalutamide-resistant prostate cancer
Author(s) -
Holger H.H. Erb,
Julia Bodenbender,
Florian Handle,
Tamara Diehl,
Lukas Donix,
Igor Tsaur,
Martin Gleave,
Axel Haferkamp,
Johannes Huber,
Susanne Fuessel,
Eva Juengel,
Zoran Čulig,
Christian Thomas
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0237248
Subject(s) - enzalutamide , prostate cancer , stat5 , gene knockdown , cancer research , lncap , medicine , stat protein , androgen receptor , pharmacology , oncology , cancer , biology , signal transduction , cell culture , stat3 , microbiology and biotechnology , genetics , receptor
Despite enzalutamide's efficacy in delaying the progression of metastatic castration-resistant prostate cancer (CRPC), resistance to this anti-androgen inevitably occurs. Several studies have revealed that the signal transducer and activator of transcription (STAT) 5 plays a role in tumour progression and development of drug resistance such as enzalutamide. Data mining revealed heterogeneous expression of STAT5 in enzalutamide-treated mCRPC patients and enzalutamide-resistant prostate cancer (PCa). Isobologram analysis revealed that the STAT5 inhibitor pimozide combined with enzalutamide has? additive and synergistic inhibitory effects on cell viability in the used models. Functional analysis with siRNA-mediated STAT5 knockdown yielded divergent results. The LNCaP-derived cell line MR49F could be resensitised to enzalutamide by siRNA-mediated STAT5b-knock-down. In contrast, neither STAT5a nor STAT5b knockdown resensitised enzalutamide-resistant LAPC4-EnzaR cells to enzalutamide. In conclusion, our results indicate that STAT5 may be a possible target in a subgroup of enzalutamide-resistant PCa. However, based on the data presented here, a general role of STAT5 in enzalutamide-resistance and its potential as a therapeutic target could not be shown.