Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: Efficacy and underlying mechanisms
| Autor: | Ashley Gragg, Xiaodong Yang, Katherine K. Matthay, Sabine Mueller, Mei Yin C. Polley, William A. Weiss, Steven G. DuBois, T. Sottero, Daphne A. Haas-Kogan, Andrew M. Davidoff, Gautam Prasad |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Radiation-Sensitizing Agents DNA repair Blotting Western Mice Nude Apoptosis Biology Hydroxamic Acids Article Histone Deacetylases Histones Mice Neuroblastoma medicine Tumor Cells Cultured Animals Humans Viability assay Vorinostat neoplasms Tumor Stem Cell Assay Cell Proliferation Cell growth Acetylation Forkhead Transcription Factors medicine.disease Flow Cytometry Combined Modality Therapy Histone Deacetylase Inhibitors Luminescent Proteins DNA Repair Enzymes Oncology Gamma Rays Cancer cell Cancer research Histone deacetylase medicine.drug |
| Popis: | Histone deacetylase (HDAC) inhibitors can radiosensitize cancer cells. Radiation is critical in high-risk neuroblastoma treatment, and combinations of HDAC inhibitor vorinostat and radiation are proposed for neuroblastoma trials. Therefore, we investigated radiosensitizing effects of vorinostat in neuroblastoma. Treatment of neuroblastoma cell lines decreased cell viability and resulted in additive effects with radiation. In a murine metastatic neuroblastoma in vivo model vorinostat and radiation combinations decreased tumor volumes compared to single modality. DNA repair enzyme Ku-86 was reduced in several neuroblastoma cells treated with vorinostat. Thus, vorinostat potentiates anti-neoplastic effects of radiation in neuroblastoma possibly due to down-regulation of DNA repair enzyme Ku-86. |
| Databáze: | OpenAIRE |
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