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
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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