Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

Wei Zhou,Jingyuan Zhang,Shanshan Jia,Ziqi Meng,Xinkui Liu,Shuyu Liu,Mengwei Ni,Jiarui Wu,Yingli Zhu,Siyu Guo

doi:10.1186/s12906-019-2787-y

Wei Zhou, Jingyuan Zhang + Show 8 more

Open Access

https://doi.org/10.1186/s12906-019-2787-y

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Abstract

BackgroundAs an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out.MethodsIn this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses.ResultsThe results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo.ConclusionThis research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

Highlights

As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out
protein-protein interaction (PPI) network of GC targets A total of 60 target proteins related to GC were retrieved from the Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), PharmGKB, disease gene search engine with evidence sentences (DigSEE), and DisGeNET databases (Additional file 2: Table S2)
Potential key target network for the treatment of GC with CKI The CKI active compound-predicted target PPI network was combined with the GC-PPI network to remove proteins that did not intersect, and the potential targets of CKI for the treatment of GC were intuitively obtained

Summary

Introduction

As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. Gastric cancer (GC) is one of the most common malignant tumors, and its mortality rate ranks third in the world, making it the fifth most frequently diagnosed cancer according to the latest report of Global Cancer Statistics (GLOBOCAN 2018). GC is often diagnosed at an advanced stage, and surgery can possibly cure patients with GC; a multimodality approach can increase survival [3]. The adverse effects of radiotherapy and chemotherapy frequently cause physical damage to patients, such as upper limb swelling on the affected side, decreased white blood cells and immunity, gastrointestinal reactions, bone marrow suppression, immune dysfunction and organ damage, causing

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