2-Deoxyglucose treatment complements the cisplatin- or BH3-only mimetic-induced suppression of neuroblastoma cell growth

被引：19

作者：

Chuang, Jiin-Haur ^{[1
,2
,3
]}

Chou, Ming-Huei ^{[2
,3
]}

Tai, Ming-Hong ^{[4
]}

Lin, Tsu-Kung ^{[1
,2
,5
]}

Liou, Chia-Wei ^{[1
,2
,5
]}

Chen, Tingya ^{[1
,2
]}

Hsu, Wen-Ming ^{[6
,7
]}

Wang, Pei-Wen ^{[1
,2
,8
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Mitochondrial Res Unit, Kaohsiung, Taiwan

[2] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Kaohsiung, Taiwan

[3] Kaohsiung Chang Gung Mem Hosp, Div Pediat Surg, Kaohsiung, Taiwan

[4] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 804, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Neurol, Kaohsiung 833, Taiwan

[6] Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan

[7] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan

[8] Kaohsiung Chang Gung Mem Hosp, Dept Internal & Nucl Med, Kaohsiung 833, Taiwan

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2013年 / 45卷 / 05期

关键词：

ABT737; Apoptosis; 2-Deoxyglucose; Glycolysis; Neuroblastoma; CANCER-CELLS; DEPENDENT APOPTOSIS; GENE-EXPRESSION; IN-VITRO; N-MYC; C-MYC; 2-DEOXY-D-GLUCOSE; GLYCOLYSIS; METABOLISM; HYPOXIA;

D O I：

10.1016/j.biocel.2013.01.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neuroblastoma (NB) is characterized by pleomorphic molecular characteristics, which may influence cellular metabolism as well as the efficacy of glycolytic inhibitors in suppressing NB cell growth. We studied the metabolic profile of four NB cell lines without or with MYCN amplification and found no unanimous metabolic characteristics. The two NB cell lines with MYCN amplification exhibited a significantly higher HIF-1 alpha expression level and ATP content compared to the two cell lines without MYCN amplification. MYCN amplification was associated with significantly greater inhibition of cellular proliferation and more apoptosis after treatment with the glycolytic inhibitor 2-deoxyglucose (2DG). Further analysis showed that 2DG increased PDK1 but decreased the ATP content and increased expression of the proapoptotic BH3-only protein Bad in both SK-N-AS (without MYCN amplification) and SK-N-DZ (with MYCN amplification) cells. In addition, 2DG decreased hexokinase II expression in SK-N-DZ cells and increased HIF-1 alpha, Noxa, and PUMA expression in SK-N-AS cells. Pretreating SK-N-DZ cells with 2DG or cisplatin for 24h, followed by cisplatin or 2DG for another 24h, resulted in significantly greater suppression of cellular proliferation compared to treatment with 2DG or cisplatin for 48 h alone. Effective suppression of SK-N-AS proliferation occurred only when the cells were pretreated with cisplatin. Pretreatment of SK-N-DZ, but not SK-N-AS, with 2DG followed by the BH3-only mimetic ABT737 also resulted in significantly greater suppression of cellular proliferation compared to treatment with ABT737 or 2DG alone. A low dose of 2DG (2 mM) was as effective as a high dose (20 mM) in SK-N-DZ cells. In conclusion, the glycolytic inhibitor 2DG complemented the cisplatin- or ABT737-induced suppression of growth in NB cells, which are sensitive to glycolytic inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：944 / 951

页数：8

共 34 条

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