组蛋白去乙酰化酶抑制剂伏立诺他联合放疗治疗转移性神经母细胞瘤：疗效和潜在机制。
Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: efficacy and underlying mechanisms.
机构信息
Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0106, USA.
出版信息
Cancer Lett. 2011 Jul 28;306(2):223-9. doi: 10.1016/j.canlet.2011.03.010. Epub 2011 Apr 16.
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.
摘要
组蛋白去乙酰化酶（HDAC）抑制剂可以使癌细胞对放射敏感。放射治疗在高危神经母细胞瘤的治疗中至关重要，因此提议将 HDAC 抑制剂伏立诺他和放射治疗联合应用于神经母细胞瘤的临床试验。因此，我们研究了伏立诺他在神经母细胞瘤中的放射增敏作用。用伏立诺他处理神经母细胞瘤细胞系会降低细胞活力，并与放射治疗产生相加作用。在一种鼠转移性神经母细胞瘤的体内模型中，与单一治疗方式相比，伏立诺他和放射治疗联合治疗可降低肿瘤体积。用伏立诺他处理几种神经母细胞瘤细胞后，DNA 修复酶 Ku-86 减少。因此，伏立诺他增强了神经母细胞瘤中放射治疗的抗肿瘤作用，可能是由于 DNA 修复酶 Ku-86 的下调。
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