Abstract
Background Tumor microenvironment (TME) takes a vital effect on the occurrence and development of cancer. Radix Rhei Et Rhizome (RRER, Da-Huang in pinyin), a classical Chinese herb, has been widely used in gastric cancer (GC) for many years in China. However, inadequate systematic studies have focused on the anti-GC effect of RRER in TME. This study intended to uncover the mechanism of it by network pharmacology. Methods We collected compounds and targets of RRER from traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. GC targets were obtained from GeneCards. Protein-protein interaction (PPI) network and RRER-GC-target network were built by STRING and Cytoscape 3.2.1. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results We obtained 92 compounds of RRER. A total of 10 key compounds and 20 key targets were selected by “RRER-GC-target network” topological analysis. GO analysis showed that the biological process mainly involved in response to the tumor necrosis factor, positive regulation of fibroblast proliferation, and DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest. Molecular functions included cyclin-dependent protein serine/threonine kinase activity, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and transmembrane receptor protein tyrosine kinase activity. Cellular components mainly were centrosome, cell surface, and membrane. KEGG pathway enrichment results mainly involved in the p53 signaling pathway, estrogen signaling pathway, and regulation of lipolysis in adipocytes. Conclusion This study explored the anti-GC mechanism of RRER from the perspective of TME based on network pharmacology, which contributed to the development and application of RRER.
Highlights
Gastric cancer (GC) remains the world’s second most common cause of cancer-related death [1]. ere are nearly 1 million new gastric cancer (GC) cases in the world each year [2]
A total of 11 842 GC targets were obtained in GeneCards
Gene Ontology (GO) analysis showed that the biological process mainly involved in response to the tumor necrosis factor, positive regulation of fibroblast proliferation, and DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Summary
Gastric cancer (GC) remains the world’s second most common cause of cancer-related death [1]. ere are nearly 1 million new GC cases in the world each year [2]. The methanol extract of RRER has the anti-GC effect by mediating cell death with an intrinsic apoptotic pathway [7]. Radix Rhei Et Rhizome (RRER, Da-Huang in pinyin), a classical Chinese herb, has been widely used in gastric cancer (GC) for many years in China. We collected compounds and targets of RRER from traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. GO analysis showed that the biological process mainly involved in response to the tumor necrosis factor, positive regulation of fibroblast proliferation, and DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest. Is study explored the anti-GC mechanism of RRER from the perspective of TME based on network pharmacology, which contributed to the development and application of RRER Conclusion. is study explored the anti-GC mechanism of RRER from the perspective of TME based on network pharmacology, which contributed to the development and application of RRER
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