Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2020; 12(10): 1091-1103
Published online Oct 15, 2020. doi: 10.4251/wjgo.v12.i10.1091
Synergistic anti-liver cancer effects of curcumin and total ginsenosides
Zhe Deng, Xiao-Yan Xu, Fenny Yunita, Qing Zhou, Yong-Rong Wu, Yu-Xing Hu, Zhi-Qi Wang, Xue-Fei Tian
Zhe Deng, Fenny Yunita, Xue-Fei Tian, Department of Internal Medicine, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
Xiao-Yan Xu, Xue-Fei Tian, Hunan Key Laboratory of Translational Research in Formulas and Zheng of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
Qing Zhou, The First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
Yong-Rong Wu, Yu-Xing Hu, School of Basic Chinese Medical Sciences, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
Zhi-Qi Wang, College of Pharmaceutical Sciences, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
Author contributions: Deng Z, Xu XY, Yunita F, Zhou Q, Wu YR, Hu YX, and Wang ZQ performed the experiments; Deng Z and Xu XY reviewed and edited the manuscript; Deng Z, Xu XY, and Yunita F designed and performed the study, conducted the statistical analysis, and wrote the paper; Tian XF conceived and designed the study. All authors read and approved the manuscript and agree to be accountable for all aspects of the research in ensuring that the accuracy and integrity of any part of the work are appropriately investigated and resolved.
Supported by the National Natural Science Foundation of China, No. 81473617; the Science and Technology Department of Hunan Province, No. 2017SK50310; and the Hunan Education Department’s Science and Research Project, No. 16K066.
Institutional animal care and use committee statement: This study was reviewed and approved by the Ethics Review Committee of Experimental Animal Welfare at the Central South University in Changsha, China.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Dataset available from the corresponding author at 003640@hnucm.edu.cn. The participants gave informed consent for data sharing.
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: Xue-Fei Tian, PhD, Professor, College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Yuelu District, Changsha 410208, Hunan Province, China. 003640@hnucm.edu.cn
Received: March 2, 2020
Peer-review started: March 2, 2020
First decision: April 25, 2020
Revised: May 18, 2020
Accepted: May 27, 2020
Article in press: May 27, 2020
Published online: October 15, 2020
Processing time: 226 Days and 1.6 Hours
ARTICLE HIGHLIGHTS
Research background

New therapeutic agents for liver cancer, which can control inflammation and restore cellular immunity, are required. Curcumin (Cur) is a natural anti-inflammatory drug and total ginsenosides (TG) are a commonly used immunoregulatory drug.

Research motivation

Both Cur and TG have been shown to exert anti-liver cancer effects. This study discussed the anti-tumor effect of Cur combined with TG in liver cancer and its molecular mechanism.

Research objectives

To determine the synergistic immunomodulatory and anti-inflammatory effects of Cur combined with TG in a mouse model of subcutaneous liver cancer.

Research methods

The changes in tumor volume and expression of relevant factors were compared in a subcutaneous liver cancer mouse model after treatment with Cur, TG, and the combination of the two drugs. The protein expression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1), inflammatory indicators Toll like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), and vascular growth-related factors nitric oxide synthases (iNOS) and matrix metalloproteinase 9 were analyzed by Western blot analysis. CD4+CD25+Foxp3+ regulatory T cells (Tregs) were counted by flow cytometry.

Research results

The combination therapy of Cur and TG significantly inhibited the growth of liver cancer, and TG showed dose dependence. Cur combined with TG-520 markedly decreased the protein expression of PD-L1 (P < 0.0001), while CD4+CD25+Foxp3+ Tregs regulated by the PD-L1 signaling pathway exhibited a positive correlation with PD-L1. Cur combined with TG-520 also inhibited the cascade action mediated by NF-κB (P < 0.0001), inhibiting the TLR4/NF-κB signaling pathway (P = 0.0088, P < 0.0001), which is associated with inflammation and acts on PD-L1. It also inhibited the NF-κB-MMP9 signaling pathway (P < 0.0001), which is associated with tumor angiogenesis.

Research conclusions

Cur combined with TG regulates immune escape through the PD-L1 pathway and inhibits liver cancer growth through NF-κB-mediated inflammation and angiogenesis.

Research perspectives

This study offers a potential combination of drugs that could improve the effectiveness of treatment for liver cancer.