Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2021; 27(10): 939-958
Published online Mar 14, 2021. doi: 10.3748/wjg.v27.i10.939
Huanglian decoction suppresses the growth of hepatocellular carcinoma cells by reducing CCNB1 expression
Min Li, Hua Shang, Tao Wang, Shui-Qing Yang, Lei Li
Min Li, Hua Shang, Department of Gastroenterology, Zibo Central Hospital, Zibo 255036, Shandong Province, China
Tao Wang, Department of General Surgery, Zibo Central Hospital, Zibo 255036, Shandong Province, China
Shui-Qing Yang, Lei Li, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
Lei Li, Department of Pathology, University of Otago, Dunedin px806, New Zealand
Author contributions: Li L conceived and performed the experiments and drafted the article; Li M and Shuang H conceived and performed partial experiments; Wang T and Yang SQ designed the study, supervised the experiments, and revised the article; all authors read and approved the final manuscript.
Institutional review board statement: Animal and human experiments were not conducted in this study.
Conflict-of-interest statement: The authors declare that there are no competing interests associated with the manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at [wshililei@buaa.edu.cn].
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: Lei Li, PhD, Academic Research, Department of Pathology, University of Otago, 270 Great King Street, Dunedin px806, New Zealand. wshililei@buaa.edu.cn
Received: November 26, 2020
Peer-review started: November 26, 2020
First decision: December 21, 2020
Revised: January 3, 2021
Accepted: February 1, 2021
Article in press: February 1, 2021
Published online: March 14, 2021
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is the third leading cause of cancer-related mortality worldwide. Huanglian decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer.

Research motivation

In recent years, the application of traditional Chinese medicine in the field of cancer treatment has increased. However, research on Huanglian decoction is still insufficient. We believe that Huanglian decoction may have the potential to treat HCC.

Research objectives

Our research aimed to clarify the effect of Huanglian decoction on HCC cells and to analyze its primary targets and potential functional pathways.

Research methods

In our study, we analyzed the regulatory network of Huanglian decoction and HCC through bioinformatics and network pharmacology and identified key genes. In vitro experiments were performed to verify the effect of Huanglian decoction on HCC cells, and the CCNB1 gene was knocked down to confirm that it is the main target of Huanglian decoction. Determination of the expression levels of key proteins verified the primary mechanism of Huanglian decoction.

Research results

Huanglian decoction can significantly inhibit the growth, migration and invasiveness of HCC cells and can also induce apoptosis and G2/M phase arrest. The results of the network pharmacological analysis showed that the main target of Huanglian decoction in HCC is CCNB1. We verified that Huanglian decoction had an inhibitory effect on liver cancer cells mainly via CCNB1 downregulation. Following Huanglian decoction treatment, the expression levels of Bax, caspase 3, caspase 9, p21 and p53 in HCC cells were increased, while the expression of CDK1 and CCNB1 was significantly decreased. Finally, the p53 signaling pathway plays an important role in this process.

Research conclusions

Huanglian decoction has a significant inhibitory effect on HCC cells. Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating CCNB1 expression to activate the p53 signaling pathway.

Research perspectives

Huanglian decoction has the potential to treat HCC, and CCNB1 is a key therapeutic target in HCC.