ZNRD1的上调通过调节ERCC1和Bcl-2增强人食管癌细胞对顺铂的耐药性。
Upregulation of ZNRD1 enhances cisplatin resistance in human esophageal cancer cells by regulation of ERCC1 and Bcl-2.
作者信息
Guo Wei, Zhao Yun-Ping, Jiang Yao-Guang, Wang Ru-Wen, Hong Liu, Fan Dai-Ming
机构信息
Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, PR China.
出版信息
Tumour Biol. 2008;29(3):188-94. doi: 10.1159/000146864. Epub 2008 Jul 22.
BACKGROUND/AIMS: The precise mechanism of the zinc ribbon domain-containing-1 (ZNRD1) gene on cisplatin resistance remains unclear. The aim of this study is to identify the gene expression profile and explore the role of these genes in ZNRD1-induced cisplatin resistance in esophageal cancer cells.
METHODS
An expression vector with ZNRD1 was transfected into the EC109 cells, and then cDNA microarray analysis was performed to identify the gene expression profile. The sensitivity of transfected EC109 cells to cisplatin was evaluated using the MTT assay. RT-PCR and Western blots were performed to validate the differential expression of genes identified by cDNA microarray analysis.
RESULTS
We identified 16 genes with significantly different expression levels between the transfected and control cells. The tolerance of EC109 cells to cisplatin was significantly enhanced by the upregulation of ZNRD1. Furthermore, the expression of excision repair cross-complementing-1 (ERCC1) and B-cell lymphoma-2 (Bcl-2) was significantly upregulated.
CONCLUSION
The ZNRD1 gene might be involved in the cisplatin resistance of EC109 cells by regulating the expression of ERCC1 and Bcl-2.
背景/目的：含锌带结构域蛋白1（ZNRD1）基因在顺铂耐药中的精确机制尚不清楚。本研究旨在鉴定基因表达谱，并探讨这些基因在ZNRD1诱导的食管癌细胞顺铂耐药中的作用。
方法
将携带ZNRD1的表达载体转染至EC109细胞，然后进行cDNA微阵列分析以鉴定基因表达谱。使用MTT法评估转染的EC109细胞对顺铂的敏感性。进行RT-PCR和蛋白质免疫印迹以验证通过cDNA微阵列分析鉴定的基因的差异表达。
结果
我们鉴定出转染细胞与对照细胞之间16个基因的表达水平存在显著差异。ZNRD1的上调显著增强了EC109细胞对顺铂的耐受性。此外，切除修复交叉互补蛋白1（ERCC1）和B细胞淋巴瘤-2（Bcl-2）的表达显著上调。
结论
ZNRD1基因可能通过调节ERCC1和Bcl-2的表达参与EC109细胞的顺铂耐药。
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