NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2022, Vol. 34 ›› Issue (10): 1784-1793. doi: 10.16333/j.1001-6880.2022.10.017

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Mechanism of Canmei Decoction in the treatment of colorectal cancer based on network pharmacology and molecular docking

ZHOU Ya-qiu1,ZHOU Hong-guang1,2*   

  1. 1Cancer Institute,the First Clinical College of Nanjing University of Chinese Medicine,Nanjing 210046,China;2Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210009,China
  • Online:2022-10-28 Published:2022-10-31

Abstract:

To explore the potential mechanism of Canmei Decoction (CMF)in the treatment of colorectal cancer based on network pharmacology,molecular docking and experimental verification.The active components of CMF were collected by TCMSP database,chemical composition database,literature mining and other methods,and candidate targets were obtained through ADME screening,and the human genes corresponding to the target proteins were queried by UniProt database;targets related to colorectal cancer were collected through GeneCards and OMIM databases,and candidate genes were obtained by extracting the intersection network.Using STRING database,the protein-protein interaction network (PPI) of intersection target was constructed,and the key target genes were selected.The common target genes were enriched by GO function and analyzed by KEGG pathway.Molecular docking technology was used to verify the docking between the core components of the compound and the key targets,and the core chemical components were experimentally verified.In vitro validation:MTT,Annexin V-FITC/PI double staining and Western blot were used to verify the inhibitory rate of different concentrations of quercetin on HCT116 cells and the expression levels of apoptosis-related proteins.Experiments obtained 166 corresponding targets for compounds contained in CMF,1 028 corresponding targets for colorectal cancer,and 79 key targets for the intersection of the two.There were 1 609 items related to biological process,41 items related to cell composition and 123 items related to molecular function in the key target GO enrichment items.KEGG enrichment pathways of key targets involve cancer pathway,PI3K-Akt signaling pathway,IL-17 signaling pathway,cell transcription,apoptosis and so on.Molecular docking results showed that the core components of CMF had a good affinity with the key targets of colorectal cancer.The results of cell experiments showed that quercetin with different concentrations could significantly inhibit cell proliferation and promote cell apoptosis,reduce the expression of anti-apoptotic protein Bcl-2 and increase the expression of pro-apoptotic protein BAX.In conclusion,the potential mechanism of CMF in the prevention and treatment of colorectal cancer may be related to the regulation of immune inflammatory response,autophagy,cell proliferation and apoptosis,and has the characteristics of multi-target,multi-path and multi-system mechanism.

Key words: Canmei Decoction, colorectal cancer, network pharmacology, mechanism of action, quercetin

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