Assessment of STAT5 as a potential therapy target in enzalutamide-resistant prostate cancer
Autor: | Erb, Holger H. H., Bodenbender, Julia, Handle, Florian, Diehl, Tamara, Donix, Lukas, Tsaur, Igor, Gleave, Martin, Haferkamp, Axel, Huber, Johannes, Fuessel, Susanne, Juengel, Eva, Culig, Zoran, Thomas, Christian |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
Cancer Treatment Biochemistry Medicine and Health Sciences STAT5 Transcription Factor Enzyme assays Colorimetric assays Cell Analysis MTT assay Prostate Cancer Prostate Diseases food and beverages Small interfering RNA Lamins Nucleic acids Gene Expression Regulation Neoplastic Bioassays and Physiological Analysis Oncology Benzamides Androgens Medicine Research Article Cell Viability Testing Urology Science Antineoplastic Agents Transfection Research and Analysis Methods Cell Line Tumor Nitriles Phenylthiohydantoin Genetics Humans Molecular Biology Techniques Non-coding RNA Molecular Biology Tumor Suppressor Proteins Biology and Life Sciences Cancers and Neoplasms Proteins Prostatic Neoplasms Hormones Gene regulation Genitourinary Tract Tumors Cytoskeletal Proteins Drug Resistance Neoplasm Biochemical analysis RNA Gene expression |
Zdroj: | PLoS ONE, Vol 15, Iss 8, p e0237248 (2020) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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