Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2017; 23(7): 1189-1202
Published online Feb 21, 2017. doi: 10.3748/wjg.v23.i7.1189
Dysregulation of mRNA profile in cisplatin-resistant gastric cancer cell line SGC7901
Xiao-Que Xie, Qi-Hong Zhao, Hua Wang, Kang-Sheng Gu
Xiao-Que Xie, Hua Wang, Kang-Sheng Gu, Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui Province, China
Qi-Hong Zhao, Department of Food and Nutrition Hygiene, School of Public Health, Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: Xie XQ performed experiments, prepared the manuscript and analyzed data; Zhao QH performed select experiments; Zhao QH and Wang H read the manuscript and gave important intellectual suggestion; Wang H and Gu KS designed and supervised the project.
Supported by Projects of Foreign Science and Technology Cooperation of Anhui Province, No. 1604b0602027; New Century Excellent Talents in University, Ministry of Education of China, No. NCET-13-0644; and Wanjiang Scholars Program of Anhui Province of China.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Anhui Medical University Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declared no conflict of interest.
Data sharing statement: Technical appendix and dataset available from the corresponding author at 13805692145@163.com. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kang-Sheng Gu, PhD, Professor, Department of Oncology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230032, Anhui Province, China. 13805692145@163.com
Telephone: +86-551-62923504
Received: October 9, 2016
Peer-review started: October 10, 2016
First decision: November 9, 2016
Revised: November 24, 2016
Accepted: December 16, 2016
Article in press: December 19, 2016
Published online: February 21, 2017
Processing time: 134 Days and 6.7 Hours
Abstract
AIM

To explore novel therapeutic target of cisplatin resistance in human gastric cancer.

METHODS

The sensitivity of SGC7901 cells and cisplatin-resistant SGC7901 cells (SGC7901/DDP) for cisplatin were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. High-quality total RNA which isolated from SGC7901/DDP cells and SGC7901 cells were used for mRNA microarray analysis. Results were analyzed bioinformatically to predict their roles in the development of cisplatin resistance and the expression of 13 dysregulated mRNAs we selected were validated by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

SGC7901/DDP cells highly resistant to cisplatin demonstrated by MTT assay. A total of 1308 mRNAs (578 upregulated and 730 downregulated) were differentially expressed (fold change ≥ 2 and P-value < 0.05) in the SGC7901/DDP cells compared with SGC7901 cells. The expression of mRNAs detected by qRT-PCR were consistent with the microarray results. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis demonstrated that the differentially expressed mRNAs were enriched in PI3K-Akt, Notch, MAPK, ErbB, Jak-STAT, NF-kappaB signaling pathways which may be involved in cisplatin resistance. Several genes such as PDE3B, VEGFC, IGFBP3, TLR4, HIPK2 and EGF may associated with drug resistance of gastric cancer cells to cisplatin.

CONCLUSION

Exploration of those altered mRNAs may provide more promising strategy in diagnosis and therapy for gastric cancer with cisplatin resistance.

Keywords: Gastric cancer; Dysregulate; Cisplatin resistance; Microarray; Biology

Core tip: We tested the sensitivity of human gastric cancer cells SGC7901/DDP and SGC7901 for cisplatin and compared their mRNA expression profile using a human mRNA microarray, and then performed bioinformatics analysis to depict comprehensively the properties of the differentially expressed mRNAs. Results demonstrated that the dysregulated mRNA were enriched in functions and pathways that may be involved in cisplatin resistance. Exploration of the dysregulated genes could suggest a promising strategy in diagnosis and therapy of gastric cancer with cisplatin resistance.