Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2015; 21(23): 7197-7207
Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7197
Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling
Yong-Bin Zheng, Gao-Chun Xiao, Shi-Lun Tong, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Zhi-Nan Hao
Yong-Bin Zheng, Gao-Chun Xiao, Shi-Lun Tong, Yu Ding, Qiu-Shuang Wang, Sheng-Bo Li, Zhi-Nan Hao, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Zheng YB designed the research; Xiao GC, Tong SL, Ding Y, Wang QS, Li SB and Hao ZN performed the research; Zheng YB and Xiao GC analyzed the data; Zheng YB and Tong SL wrote the paper; all authors had access to the data, attested to the validity of the results, and approved the final article.
Supported by National Natural Science Foundation of China, No. 81372553.
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: Yong-Bin Zheng, MD, Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan 430060, Hubei Province, China. yongbinzhengx@163.com
Telephone: +86-25-2810566 Fax: +86-25-2810568
Received: October 15, 2014
Peer-review started: October 15, 2014
First decision: October 18, 2014
Revised: December 11, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: June 21, 2015
Processing time: 247 Days and 21.6 Hours
Abstract

AIM: To examine the potential anti-tumor activity of paeoniflorin in the human gastric carcinoma cell line MGC-803.

METHODS: Cell viability and cytotoxic effects in MGC-803 cells were analyzed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay, respectively. Cell apoptosis of MGC-803 cells was measured using flow cytometry, DAPI staining assay and caspase-3 activity assay. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of microRNA-124 (miR-124) in response to paeoniflorin. The expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phospho-Akt (p-Akt) and phospho-signal transducer and activator of transcription 3 (p-STAT3) were also measured by quantitative RT-PCR and Western blot analysis in normal, miR-124 and anti-miR-124 over-expressing MGC-803 cells, treated with paeoniflorin.

RESULTS: Paeoniflorin was found to inhibit MGC-803 cell viability in a dose-dependent manner. Paeoniflorin treatment was associated with the induction of apoptosis and caspase-3 activity in MGC-803 cells. Paeoniflorin treatment significantly increased miR-124 levels and inhibited the expression of PI3K, Akt, p-Akt and p-STAT3 in MGC-803 cells. Interestingly, the over-expression of miR-124 inhibits PI3K/Akt and phospho-STAT3 expressions in MGC-803 cells. PI3K agonist (IGF-1, 1 μg/10 μL) or over-expression of STAT3 reversed the effect of paeoniflorin on the proliferation of MGC-803 cells. Over-expression of anti-miR-124 in MGC-803 cells reversed paeoniflorin-induced up-regulation.

CONCLUSION: In summary, the in vitro data suggest that paeoniflorin is a potential novel therapeutic agent against gastric carcinoma, which inhibits cell viability and induces apoptosis through the up-regulation of miR-124 and suppression of PI3K/Akt and STAT3 signaling.

Keywords: Gastric cancer; Paeoniflorin; MicroRNA-124; Phosphatidylinositol 3-kinase; Akt; Signal transducer and activator of transcription 3

Core tip: The in vitro data suggest that paeoniflorin is a potential novel therapeutic agent against gastric carcinoma, which inhibits cell viability and induces apoptosis through the up-regulation of microRNA-124 and suppression of phosphatidylinositol 3-kinase/Akt signaling.