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基于网络药理学和实验验证的茯苓酸治疗胃癌的机制

Mechanism of pachymic acid in the treatment of gastric cancer based on network pharmacology and experimental verification.

作者信息

Du Yu-Hua, Zhao Jian-Jun, Li Xia, Huang Shi-Cong, Ning Na, Chen Guo-Qing, Yang Yi, Nan Yi, Yuan Ling

机构信息

College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China.

Ningxia Chinese Medicine Research Center, Manufacturing Laboratory, Yinchuan 750004, Ningxia Hui Autonomous Region, China.

出版信息

World J Gastrointest Oncol. 2024 Jan 15;16(1):30-50. doi: 10.4251/wjgo.v16.i1.30.

DOI:10.4251/wjgo.v16.i1.30
PMID:38292852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10824110/
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 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 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 cell studies, which serve as benchmarks for further research.

摘要

背景

茯苓酸(PA)来源于茯苓。PA对多种肿瘤具有多种药理作用和抑制作用。然而,PA在胃癌(GC)中的作用机制仍不清楚。

目的

采用网络药理学与实验验证相结合的方法,研究PA治疗GC的机制。

方法

利用GeneCards和OMIM数据库获取GC靶点,同时利用Pharm Mapper数据库获取PA靶点。利用STRING数据库构建蛋白质-蛋白质相互作用网络并筛选核心靶点。进行基因本体论、京都基因与基因组百科全书(KEGG)分析和基因集富集分析,并对核心靶点进行分子对接和临床相关性分析。最终,通过细胞实验对网络药理学研究结果进行验证,包括细胞活力、凋亡、细胞周期、克隆及蛋白质免疫印迹分析等评估。

结果

通过网络药理学分析筛选出核心靶点,KEGG富集分析表明PI3K/AKT信号通路可能是PA有效治疗GC的作用机制。实验结果表明,PA可调控PI3K/AKT信号通路,从而抑制GC细胞增殖、诱导凋亡并使细胞周期停滞。

结论

网络药理学研究表明,PA可通过调控多种信号通路、作用于多种靶点来治疗GC。细胞实验也支持了这一结论,可为进一步研究提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/1df6c020d108/WJGO-16-30-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/c5fb09014861/WJGO-16-30-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/3de514c28d9f/WJGO-16-30-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/0b9786a49a0b/WJGO-16-30-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/650fc4ac6b05/WJGO-16-30-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/12caf04e18eb/WJGO-16-30-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/ba4171ccfbe9/WJGO-16-30-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/1df6c020d108/WJGO-16-30-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/c5fb09014861/WJGO-16-30-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/3de514c28d9f/WJGO-16-30-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/0b9786a49a0b/WJGO-16-30-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/650fc4ac6b05/WJGO-16-30-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/12caf04e18eb/WJGO-16-30-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/ba4171ccfbe9/WJGO-16-30-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0f2/10824110/1df6c020d108/WJGO-16-30-g007.jpg

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