Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: efficacy and underlying mechanisms

HDAC 抑制剂伏立诺他联合放射治疗转移性神经母细胞瘤:疗效及潜在机制

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作者:Sabine Mueller, Xiaodong Yang, Theo L Sottero, Ashley Gragg, Gautam Prasad, Mei-Yin Polley, William A Weiss, Katherine K Matthay, Andrew M Davidoff, Steven G DuBois, Daphne A Haas-Kogan

Abstract

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.

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