Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2024; 16(1): 30-50
Published online Jan 15, 2024. doi: 10.4251/wjgo.v16.i1.30
Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification
Yu-Hua Du, Jian-Jun Zhao, Xia Li, Shi-Cong Huang, Na Ning, Guo-Qing Chen, Yi Yang, Yi Nan, Ling Yuan
Yu-Hua Du, Jian-Jun Zhao, Xia Li, Shi-Cong Huang, Na Ning, Guo-Qing Chen, Ling Yuan, College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Xia Li, Ningxia Chinese Medicine Research Center, Manufacturing Laboratory, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yi Yang, College of Foundation, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yi Nan, Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Co-corresponding authors: Yi Nan and Ling Yuan.
Author contributions: Du YH carried out most of the studies, analyzed the data and wrote the manuscript; Nan Y designed the study and revised the manuscript; Huang SC, Ning N, and Chen GQ wrote the manuscript and carried out the chart-making work; Li X and Yang Y performed parts of the experiments and conducted statistical analyses of the data; Yuan L supervised the process of research and provided clinical guidance; Yuan L and Zhao JJ provided the conceptual and technical guidance as well as revised the manuscript critically for important intellectual content; and all authors have read and approved the manuscript. Yuan L and Nan Y have guided this research throughout the whole process, provided technical and theoretical support for this research, and made great contributions.
Supported by Ningxia Science and Technology Benefiting People Program, No. 2022CMG03064; National Natural Science Foundation of China, No. 82260879; Ningxia Natural Science Foundation, No. 2022AAC03144 and 2022AAC02039.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Ningxia Medical University (No. 2023-002).
Clinical trial registration statement: Our research does not involve clinical trial.
Informed consent statement: All of our experiments are designed and performed only in the laboratory. We didn’t test clinical sample data, no informed consent is required.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data generated or analyzed during this study are included in this paper, and further inquiries can be directed to the corresponding author (20080017@nxmu.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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ling Yuan, PhD, Professor, College of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, Ningxia Hui Autonomous Region, China. 20080017@nxmu.edu.cn
Received: July 29, 2023
Peer-review started: July 29, 2023
First decision: September 25, 2023
Revised: October 7, 2023
Accepted: November 2, 2023
Article in press: November 2, 2023
Published online: January 15, 2024
Abstract
BACKGROUND

Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear.

AIM

To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.

METHODS

The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis.

RESULTS

According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle.

CONCLUSION

Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research.

Keywords: Pachymic acid, Gastric cancer, Network pharmacology, Enrichment analysis, Cell proliferation

Core Tip: Pachymic acid (PA) is an important bioactive component of Poria cocos. Network pharmacology analysis showed that the core targets of PA in treating gastric cancer (GC) were proto-oncogene tyrosine-protein kinase Src, mitogen-activated protein kinase 1, phosphatidylinositol 3-kinase regulatory subunit alpha, heat shock protein 90-alpha, and tyrosine-protein phosphatase non-receptor type 11. Molecular docking results showed that PA could combine well with the core targets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis suggested that the PI3K/AKT signaling pathway was possible for treating GC with PA. The experiment results demonstrated that PA could decrease the survival rate of HGC-27 cells, halt the progression of the cell cycle, enhance cell apoptosis, control the PI3K/AKT signaling pathway to stimulate apoptosis, and impede cell growth.