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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2023; 15(3): 504-522
Published online Mar 15, 2023. doi: 10.4251/wjgo.v15.i3.504
Possible mechanisms associated with immune escape and apoptosis on anti-hepatocellular carcinoma effect of Mu Ji Fang granules
Yi-Bing Zhang, Yong-Rui Bao, Shuai Wang, Tian-Jiao Li, He Tai, Jia-Peng Leng, Xin-Xin Yang, Bo-Cai Wang, Xian-Sheng Meng
Yi-Bing Zhang, Yong-Rui Bao, Shuai Wang, Tian-Jiao Li, He Tai, Jia-Peng Leng, Xin-Xin Yang, Bo-Cai Wang, Xian-Sheng Meng, College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, Liaoning Province, China
Yi-Bing Zhang, Department of Clinical Trail Institution Office, Dalian Municipal Central Hospital, Dalian 116033, Liaoning Province, China
Yong-Rui Bao, Shuai Wang, Tian-Jiao Li, Xian-Sheng Meng, Technical Innovation Center of Multidimensional Analysis of Traditional Chinese Medicine of Liaoning Province, Dalian 116600, Liaoning Province, China
Yong-Rui Bao, Shuai Wang, Tian-Jiao Li, Xian-Sheng Meng, Engineering Laboratory of Modern Chinese Medicine Research of Liaoning Province, Dalian 116600, Liaoning Province, China
Author contributions: Zhang YB, Bao YR, Wang S, Wang BC and Meng XS contributed to conception and design of the study; Zhang YB, Wang S, Li TJ, Tai H, Leng JP, Wang BC and Yang XX conducted the experiments, organized the database, carried out the statistical analysis and drafted the manuscript; All authors contributed to manuscript revision, and approved the submitted version.
Supported by National Natural Science Foundation of China, No. 81874342; and Natural Science Foundation of Liaoning Province, No. 2020-MZLH-35.
Institutional animal care and use committee statement: All experimental procedures were performed with the approval of the animal guidelines and protocols established by the Medicine Ethics Review Committee of Animal Experiments of Liaoning University of Traditional Chinese Medicine. The study was reviewed and approved by the Animal Ethics Committee of The Affiliated Hospital of Liaoning University of TCM. [Approval No. 2019YS(DW)-033-01].
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data are available from the corresponding authors upon request (
mxsvvv@163.com).
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Xian-Sheng Meng, PhD, Dean, Professor, College of Pharmacy, Liaoning University of Traditional Chinese Medicine, No. 77 Life one Road, DD Port, Jinpu District, Dalian 116600, Liaoning Province, China.
mxsvvv@163.com
Received: December 20, 2022
Peer-review started: December 20, 2022
First decision: January 9, 2023
Revised: January 19, 2023
Accepted: March 2, 2023
Article in press: March 2, 2023
Published online: March 15, 2023
Processing time: 84 Days and 16 Hours
ARTICLE HIGHLIGHTS
Research background
Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers with high mortality rates worldwide.
Research motivation
Considerable effort has been expended in understanding the mechanism of Mu Ji Fang Granules (MJF) on tumor immunology in the treatment of HCC.
Research objectives
Our study explored the mechanism of MJF adjusting immune escape and apoptosis.
Research methods
We conducted Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight- Mass Spectrometry to identify the absorbable ingredients of MJF, and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis. Both in vivo and in vitro experiments were demonstrated, and multiply processes including Histopathological analysis, Immunosorbent Assay, RT-qPCR, Western blotting assays were to adopted to explore the function MJF inhibits HCC.
Research results
We found that MJF improved body weight gain and tumor inhibition rate in H22 tumor-bearing mice, protected immune organs and liver function, reduced the HCC indicator alpha-fetoprotein, affected immunity and apoptosis, and up-regulated the Transforming growth factor β1(TGF-β1)/SMAD signaling pathway, by increasing the relative expression of TGF-β1, SMAD2, p-SMAD2 and SMAD4 and decreasing SMAD7, reducing immune factors Tumor necrosis factor α and Interferon gamma, decr-easing apoptosis cytokines Fas, FasL and Bcl2/Bax, and inhibiting the effect of LY364947 in HepG2 cells.
Research conclusions
Our findings suggested that MJF inhibits HCC by activating the TGF-β1/SMAD signaling pathway, and affecting immune and apoptotic cytokines.
Research perspectives
Considerable effort has been expended in understanding the anti-HCC mechanism of MJF, all of which due to MJF’s particular participate in adjusting immune escape and apoptosis.
