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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats
Yu Wang, Hei-Ying Jin, Ming-Zhi Fang, Xiao-Feng Wang, Hao Chen, Shu-Liang Huang, De-Song Kong, Min Li, Xiu Zhang, Yu Sun, Shui-Ming Wang
Yu Wang, Ming-Zhi Fang, Min Li, Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Hei-Ying Jin, Department of Colorectal Surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Xiao-Feng Wang, Hao Chen, Shui-Ming Wang, National Center of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Shu-Liang Huang, Department of Pathology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
De-Song Kong, Scientific Research Administration Department, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Xiu Zhang, Endoscopy Center, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China
Yu Sun, Origin Bioscience Inc, Nanjing 210000, Jiangsu Province, China
Author contributions: Wang Y and Wang SM conceived and designed the study; Jin HY, Fang MZ, Wang XF, and Chen H performed the experiments; Wang Y, Li M, and Kong DS wrote the article; Huang SL, Zhang X, and Sun Y coordinated the study and analyzed the data; all the authors contributed to, read, and approved the final manuscript.
Supported by Nursing Advantage Discipline Construction Project Foundation of Jiangsu Province University, No. 2019YSHL107; Nanjing Medical Science and Technique Development Foundation, No. NWQR-201705.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Southeast University (IACUC protocol number: 20161201006.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Shui-Ming Wang, MD, PhD, Attending Doctor, Research Scientist, National Center of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157, Daming Road, Qinhuai District, Nanjing 210001, Jiangsu Province, China. watershuiming@hotmail.com
Received: November 20, 2019
Peer-review started: November 20, 2019
First decision: January 7, 2020
Revised: February 13, 2020
Accepted: March 11, 2020
Article in press: March 11, 2020
Published online: May 7, 2020
ARTICLE HIGHLIGHTS
Research background
“Tea polyphenols” is a general term for more than 30 polyphenols in tea, of which epigallocatechin gallate (EGCG) is the main compound. In recent years, a large number of studies have demonstrated that EGCG is a highly effective, biologically active, non-toxic, naturally extracted compound. Its antitumor effect and mechanism of action are constantly being clarified, and they have become a hot topic of research today. However, most of the existing studies only use cell experiments to explain its inhibitory effect.
Research motivation
The aim of our research was to explore whether EGCG can inhibit the occurrence of dimethylhydrazine (DMH)-induced rat intestinal cancer in vivo in rats. We combined bioinformatic data analysis technology to explain the common targets and significant differential genes of EGCG and colorectal cancer (CRC) for the first time and analyze the mechanism of EGCG in CRC at the molecular gene level.
Research objectives
To, using animal experiments and network pharmacological analysis, discover the inhibitory mechanism of EGCG on CRC cell proliferation and clarify its pharmacological targets.
Research methods
DMH (40 mg/kg) was used to induce CRC in rats twice weekly for 8 wk. Then, different doses of EGCG were administered (50, 100, or 200 mg/kg for 8 wk). Rats were euthanized at week 12 and week 20 to observe aberrant crypt foci and tumor formation. We used bioinformatic analysis to predict the pathways altered by EGCG in CRC.
Research results
We discovered that different doses of EGCG had inhibitory effects on aberrant crypt foci and tumors in rats and, as the dose increased, EGCG was more effective in the suppression of tumor formation. Using bioinformatics, we identified 78 target genes that were common to EGCG and CRC and 28 of the 78 genes were identified to have significant differential expression. Using KEGG and GO analyses, we found that EGCG regulated CRC, p53, PI3K-Akt, I-kappaB kinase/NF-kappaB, apoptosis, and mitogen-activated protein kinase signaling pathways.
Research conclusions
EGCG can inhibit DMH-induced CRC tumor formation in rats. Moreover, the effect of EGCG positively correlated with dose and treatment duration. This reveals the clinical treatment potential of EGCG for CRC. Our findings reveal the potential mechanisms of action and pathways of EGCG in CRC.
Research perspectives
In the future, azoxymethane, which is more potent and stable than DMH, could be used as it has the ability to induce tumor formation in a short time. Additionally, in vitro studies using cell lines would be beneficial to verify the target genes and pathways of EGCG in CRC.
