期刊论文详细信息
BMC Cancer
GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells
Research Article
Vinod Vijay Subhash1  Wei Peng Yong2  Shi Hui Tan3  Robert Lim3  Woei Loon Tan3  Zee Ying Kiat3  Foong Ying Wong3  Mei Shi Yeo3  Chen Xie3 
[1] Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore;Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore;Department of Haematology-Oncology, National University Hospital of Singapore, Singapore, Singapore;Department of Haematology-Oncology, National University Hospital of Singapore, Singapore, Singapore;
关键词: GTSE1;    Drug resistance;    Cisplatin;    Apoptosis;   
DOI  :  10.1186/s12885-015-1550-0
 received in 2015-04-30, accepted in 2015-07-14,  发布年份 2015
来源: Springer
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【 摘 要 】

BackgroundPlatinum based therapy is commonly used in the treatment of advanced gastric cancer. However, resistance to chemotherapy is a major challenge that causes marked variation in individual response rate and survival rate. In this study, we aimed to identify the expression of GTSE1 and its correlation with cisplatin resistance in gastric cancer cells.MethodsMethylation profiling was carried out in tissue samples from gastric cancer patients before undergoing neoadjuvent therapy using docetaxel, cisplatin and 5FU (DCX) and in gastric cancer cell lines. The correlation between GTSE1 expression and methylation in gastric cancer cells was determined by RT-PCR and MSP respectively. GTSE1 expression was knocked-down using shRNA’s and its effects on cisplatin cytotoxicity and cell survival were detected by MTS, proliferation and clonogenic survival assays. Additionally, the effect of GTSE1 knock down in drug induced apoptosis was determined by western blotting and apoptosis assays.ResultsGTSE1 exhibited a differential methylation index in gastric cancer patients and in cell lines that correlated with DCX treatment response and cisplatin sensitivity, respectively. In-vitro, GTSE1 expression showed a direct correlation with hypomethylation. Interestingly, Cisplatin treatment induced a dose dependent up regulation as well as nuclear translocation of GTSE1 expression in gastric cancer cells. Knock down of GTSE1 enhanced cisplatin cytotoxity and led to a significant reduction in cell proliferation and clonogenic survival. Also, loss of GTSE1 expression caused a significant increase in P53 mediated apoptosis in cisplatin treated cells.ConclusionOur study identifies GTSE1 as a biomarker for cisplatin resistance in gastric cancer cells. This study also suggests the repressive role of GTSE1 in cisplatin induced apoptosis and signifies its potential utility as a therapeutic target for better clinical management of gastric cancer patients.

【 授权许可】

Unknown   
© Subhash et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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