The effect of adenovirus-conjugated NDRG2 on p53-mediated apoptosis of hepatocarcinoma cells through attenuation of nucleotide excision repair capacity
The effect of adenovirus-conjugated NDRG2 on p53-mediated apoptosis of hepatocarcinoma cells through attenuation of nucleotide excision repair capacity
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腺病毒缀合的NDRG2通过减弱核苷酸切除修复能力对p53介导的肝癌细胞凋亡的影响
DOI：
10.1016/j.biomaterials.2013.09.096
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发表时间：
2014-01-01
期刊：
影响因子：
14
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Cao, Wei;Zhang, Ju-liang;Zhang, Jian
NDRG2 mRNA 和蛋白质水平可以以 p53 依赖性方式上调。 NDRG2 增强 p53 介导的细胞凋亡，而 NDRG2 的过度表达则抑制肿瘤细胞生长，无论 p53 是否突变。然而，NDRG2 抑制肿瘤细胞生长并增强 p53 介导的细胞凋亡的复杂机制尚不完全清楚。在这里，我们证明 Ad-NDRG2 增强 HepG2 细胞（野生型 p53）的凋亡。此外，Ad-NDRG2联合rAd-p53增强了化疗后Huh7细胞（突变型p53）的凋亡，并且在此过程中ERCC6基因（科凯恩综合征B组蛋白基因）的表达受到抑制。 Ad-NDRG2联合rAd-p53诱导肿瘤细胞（HepG2和Huh7细胞）凋亡；然而，转染ERCC6后细胞凋亡减弱。我们的结果表明，Ad-NDRG2 通过减弱核苷酸切除修复能力（即下调 ERCC6）来增强 p53 介导的肝癌细胞（HepG2 和 Huh7）凋亡，而 ERCC6 是 NDRG2 诱导的靶基因，参与 p53 介导的凋亡途径。 Crown 版权所有 (C) 2013 由 Elsevier Ltd 出版。保留所有权利。
NDRG2 mRNA and protein levels can be upregulated in a p53-dependent manner. NDRG2 enhances p53-mediated apoptosis, whereas overexpression of NDRG2 suppresses tumor cell growth, regardless of whether p53 is mutated. However, the complicated mechanism by which NDRG2 suppresses tumor cell growth and enhances apoptosis mediated by p53 is not fully understood. Here, we demonstrated that Ad-NDRG2 enhanced the apoptosis of HepG2 cells (wild-type p53). Additionally, Ad-NDRG2 combined with rAd-p53 enhanced the apoptosis of Huh7 cells (mutant p53) after chemotherapy, and the expression of the ERCC6 gene (Cockayne syndrome group B protein gene) was suppressed in this process. Ad-NDRG2 combined with rAd-p53 induced the apoptosis of tumor cells (HepG2 and Huh7 cells); however, apoptosis was attenuated after transfection with ERCC6. Our results indicate that Ad-NDRG2 enhances the p53-mediated apoptosis of hepatocarcinoma cells (HepG2 and Huh7) by attenuating the nucleotide excision repair capacity (i.e., by downregulating ERCC6), and ERCC6 is a NDRG2-inducible target gene that is involved in the p53-mediated apoptosis pathway. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.