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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells

Authors: Vinod Vijay Subhash, Shi Hui Tan, Woei Loon Tan, Mei Shi Yeo, Chen Xie, Foong Ying Wong, Zee Ying Kiat, Robert Lim, Wei Peng Yong

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Platinum 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.

Methods

Methylation 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.

Results

GTSE1 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.

Conclusion

Our 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.
Appendix
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Metadata
Title
GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells
Authors
Vinod Vijay Subhash
Shi Hui Tan
Woei Loon Tan
Mei Shi Yeo
Chen Xie
Foong Ying Wong
Zee Ying Kiat
Robert Lim
Wei Peng Yong
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1550-0

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