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
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is one of the most serious malignant tumors of the digestive tract, with high morbidity and mortality. In recent years, more and more evidence has shown that natural ingredients from traditional Chinese medicine can prevent and inhibit the occurrence and development of GC, showing great therapeutic potential.

Research motivation

Network pharmacology is used to predict the targets and pathways of drugs in the treatment of diseases, and the method of experimental verification is used to verify them, which provides an effective reference for further elucidating the molecular mechanism of natural products in the treatment of GC.

Research objectives

To find the possible targets and pathways of pachymic acid (PA) in the treatment of GC, and to explore the molecular mechanism of PA promoting apoptosis and arresting cell cycle of GC cells by regulating PI3K/AKT signal transduction.

Research methods

Using the TCMSP database to find the components of Poria cocos, we identified PA in Poria cocos as a potential effective component in the treatment of GC. The PharmMapper database was used to find the related targets of PA, and the GENECARDS and OMIM databases were used to find the related targets of GC, and the common targets were found by intersection. The protein-protein interaction network was constructed, and the top five core targets were screened according to the degree value. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were used to identify related pathways. Molecular docking and clinical correlation studies were used to explore the effects of core targets on GC. Cell Counting Kit-8, colony formation assay and flow cytometry were used to detect cell function indexes. Western blot was used to determine the effect of PA on PI3K/AKT signaling pathway and apoptosis pathway.

Research results

A total of 217 possible targets of PA in the treatment of GC were identified by network pharmacology, and the top five core targets were found: Proto-oncogene tyrosine-protein kinase Src, mitogen-activated protein kinase 1, phosphatidylinositol 3-kinase regulatory subunit alpha, heat shock protein 90-alpha, tyrosine-protein phosphatase non-receptor type 11. KEGG pathway analysis showed that PI3K/AKT signaling pathway was a possible pathway for the treatment of GC. Molecular docking results showed that the binding energy between PA and PI3KR1 was the highest (-8.8 kcal/mol). Experiments on HGC-27 cells confirmed that PA could inhibit the proliferation of GC cells, promote the apoptosis of cells and arrest their G0/G1 phase. Western blot results showed that PA decreased the expression of phosphorylated PI3K and AKT in GC cells, and also had an effect on apoptosis-related proteins.

Research conclusions

The inhibitory effect of PA on GC proliferation and its potential to induce apoptosis of GC cells were confirmed by network pharmacological analysis and experimental verification.

Research perspectives

PA have shown high efficiency and low toxicity in the treatment of GC. However, PA have not been truly developed into relevant drugs for clinical trials, and there is still a long way to go for the application of PA in the clinical treatment of GC. In the future, we look forward to making the treatment of GC more in-depth through more studies on the effectiveness of PA on GC and providing more treatment options for patients with GC.