Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2017; 23(15): 2716-2722
Published online Apr 21, 2017. doi: 10.3748/wjg.v23.i15.2716
Role of Δ133p53 isoform in NF-κB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells
Hong-Mei Zhang, Xiao-Guang Sang, Yan-Ze Wang, Can Cui, Li Zhang, Wan-Sheng Ji
Hong-Mei Zhang, Li Zhang, Wan-Sheng Ji, Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China
Xiao-Guang Sang, Department of Gastroenterology, Shouguang People’s Hospital, Weifang 262700, Shandong Province, China
Yan-Ze Wang, Can Cui, Graduate School of Weifang Medical University, Weifang 261042, Shandong Province, China
Author contributions: Zhang HM and Ji WS designed experiments; Zhang HM and Sang XG contributed most reagents; Sang XG, Wang YZ, Cui C and Zhang L performed research; Wang YZ, Cui C and Zhang L analyzed data; and Zhang HM and Ji WS wrote the paper.
Supported by Shandong Provincial Award Foundation for Youth and Middle-aged Scientist, No. BS2010SW034.
Institutional review board statement: The study design and conduct conformed to the Declaration of Helsinki, and was approved by the Ethics Committee of the Affiliated Hospital of Weifang Medical University.
Conflict-of-interest statement: All of the authors declare that they have no competing interests regarding this paper.
Data sharing statement: The data and materials can be obtained on request from the authors.
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. Wan-Sheng Ji, Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China. wanshengji68@126.com
Telephone: +86-536-3081251 Fax: +86-536-8650309
Received: December 2, 2016
Peer-review started: December 6, 2016
First decision: January 19, 2017
Revised: February 14, 2017
Accepted: March 15, 2017
Article in press: March 15, 2017
Published online: April 21, 2017
Processing time: 138 Days and 19.2 Hours
Abstract
AIM

To investigate the role of Δ133p53 isoform in nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells.

METHODS

The growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Δ133p53, p53β, and the NF-κB p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose-dependent manner by co-treatment with PDTC (P < 0.01).

RESULTS

RT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Δ133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P < 0.01), whereas p53β mRNA expression was not altered by PDTC treatment (P > 0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P < 0.01). Pearson correlation analysis demonstrated that Δ133p53 and p65 mRNA expression levels were positively related, while no significant relationship was observed between those of p65 and p53β (r = 0.076, P > 0.01).

CONCLUSION

Δ133p53 isoform (not p53β) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.

Keywords: Gastric cancer; p53 isoforms; Nuclear factor-κB

Core tip: Intestinal-type of gastric cancer develops from chronic gastritis. Δ133p53 isoform has been recently identified as an oncogenic actor that is pivotal in Helicobacter pylori-driven progression of chronic gastritis to gastric cancerogenesis. These results suggest that Δ133p53 isoform is required in pyrrolidine dithiocarbamate-induced inhibition of MKN45 gastric cancer cells, and disturbance in the cross-talk between p53 and nuclear factor-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies against intestinal-type gastric cancer.