Valproic acid suppresses Warburg effect and tumor progression in neuroblastoma
Valproic acid suppresses Warburg effect and tumor progression in neuroblastoma
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丙戊酸抑制神经母细胞瘤中的 Warburg 效应和肿瘤进展
DOI：
10.1016/j.bbrc.2018.11.103
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发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
Tong, Qiangsong
中科院分区：
文献类型：
--
作者：
Fang, Erhu;Wang, Jianqun;Tong, Qiangsong
葡萄糖代谢改变是癌症的一个标志，其特征是一种独特的代谢表型，称为Warburg效应或有氧糖酵解。新的研究表明丙戊酸（VPA）是一种已建立的组蛋白去乙酰化酶抑制剂，具有肿瘤抑制特性。然而，VPA在儿童最常见的颅内外恶性肿瘤神经母细胞瘤（neuroblastoma， NB）中调控Warburg效应的作用尚不明确。在这项研究中，我们发现VPA通过减少葡萄糖摄取和减少乳酸和ATP的产生来抑制NB细胞的有氧糖酵解。从机制上说，VPA通过降低E2F转录因子1 （E2F1）的水平来抑制有氧糖酵解，从而抑制糖酵解基因葡萄糖-6-磷酸异构酶（GPI）和磷酸甘油酸松酶1 （PGK1）的表达。抢救实验表明，VPA通过下调E2F1抑制有氧糖酵解和NB进展。这些结果表明，VPA抑制Warburg效应和肿瘤进展，为NB提供了一种新的治疗策略。(C) 2018爱思唯尔公司版权所有。
Altered glucose metabolism is a hallmark for cancer, which is characterized by a unique metabolic phenotype known as Warburg effect or aerobic glycolysis. Emerging studies show that valproic acid (VPA), an established histone deacetylase inhibitor, possesses tumor suppressive properties. However, the effects of VPA on the regulation of Warburg effect in neuroblastoma (NB), the most common extracranial malignancy in childhood, still remain elusive. In this study, we show that VPA inhibits the aerobic glycolysis in NB cells by decreasing glucose uptake and reducing lactate and ATP production. Mechanistically, VPA suppresses aerobic glycolysis via reducing the levels of E2F transcription factor 1 (E2F1), resulting in repressed expression of glycolytic genes glucose-6-phosphate isomerase (GPI) and phosphoglycerate pinase 1 (PGK1). Rescue experiments show that VPA inhibits the aerobic glycolysis and NB progression through down-regulation of E2F1. These results demonstrate that VPA suppresses the Warburg effect and tumor progression, indicating a novel therapeutic strategy for NB. (C) 2018 Elsevier Inc. All rights reserved.