Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2017; 23(10): 1796-1803
Published online Mar 14, 2017. doi: 10.3748/wjg.v23.i10.1796
ECRG2 enhances the anti-cancer effects of cisplatin in cisplatin-resistant esophageal cancer cells via upregulation of p53 and downregulation of PCNA
Xin-Fang Hou, Lin-Ping Xu, Hai-Yan Song, Shuai Li, Chen Wu, Ju-Feng Wang
Xin-Fang Hou, Shuai Li, Chen Wu, Ju-Feng Wang, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China
Lin-Ping Xu, Department of Science and Research, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China
Hai-Yan Song, Key Laboratory for Medical Tissue Regeneration of Henan Province, College of Basic Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Supported by the Public Welfare Project Foundation of Henan Province, No. 20130010.
Institutional review board statement: The study was reviewed and approved by the Henan Cancer Hospital Institutional Review Board.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: There are no additional data available in relation to this manuscript.
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: Dr. Ju-Feng Wang, Professor, Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou 450008, Henan Province, China. 13783583966@163.com
Telephone: +86-371-65587598 Fax: +86-371-65587598
Received: November 30, 2016
Peer-review started: December 2, 2016
First decision: December 19, 2016
Revised: January 6, 2017
Accepted: January 18, 2017
Article in press: January 18, 2017
Published online: March 14, 2017
Abstract
AIM

To explore the anti-tumor effects of esophageal cancer-related gene 2 (ECRG2) in combination with cisplatin (DDP) in DDP-resistant esophageal cancer cells (EC9706/DDP).

METHODS

A drug-resistant cell model was established, with EC9706/DDP cells being treated with ECRG2 and/or DDP. Cell viability was examined by MTT assay. The rate of cell apoptosis was determined by flow cytometry. The mRNA expression levels of proliferating cell nuclear antigen (PCNA), metallothionein (MT), and p53 were determined by RT-PCR and PCNA, while MT and p53 protein expression levels were determined by western blotting.

RESULTS

The anti-proliferative effect of ECRG2 in combination with DDP was superior when compared to ECRG2 or DDP alone. The inhibition rate for the combination reached its peak (51.33%) at 96 h. The early apoptotic rates of the control, ECRG2 alone, DDP alone, and ECRG2 plus DDP groups were 5.71% ± 0.27%, 12.68% ± 0.61%, 14.15% ± 0.87%, and 27.96% ± 0.36%, respectively. Although all treatment groups were significantly different from the control group (P < 0.05), the combination treatment of ECRG2 plus DDP performed significantly better when compared to either ECRG2 or DDP alone (P < 0.05). The combination of ECRG2 and DDP significantly upregulated p53 mRNA and protein levels and downregulated PCNA mRNA and protein levels compared to ECRG2 or DDP alone (P < 0.05). However, no changes were seen in the expression of MT mRNA or protein.

CONCLUSION

ECRG2 in combination with DDP can inhibit viability and induce apoptosis in esophageal cancer DDP-resistant cells, possibly via upregulation of p53 expression and downregulation of PCNA expression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP.

Keywords: Esophageal cancer related-gene 2, Cisplatin, Resistance, p53, Proliferating cell nuclear antigen

Core tip: Cisplatin (DDP) is one of the most effective agents in treating esophageal cancer, but drug resistance poses a major impediment. Combination therapy has become an important method for overcoming drug resistance. This study showed that esophageal cancer-related gene 2 (ECRG2) in combination with DDP can inhibit viability and induce apoptosis in DDP-resistant esophageal cancer cells, possibly via upregulation of p53 expression and downregulation of proliferating cell nuclear antigen expression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP.