Mechanism of cinnamaldehyde combined with curcumin against hepatocellular carcinoma based on network pharmacology,molecular docking and experimental study
[Objective]To study the mechanism of cinnamaldehyde combined with curcumin against hepatocellular carcinoma based on network pharmacology and molecular docking and experiments.[Methods]Pharm Mapper,Swiss Target,Target Net were used to screen the related targets of curcumin and cinnamaldehyde.TTD,Gene cards and OMIM databases were used to screen the target of liver cancer.Venny software was used to screen common targets.Enrichment analysis of gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was carried out through DAVID database,and molecular docking was carried out.MTT assay,Hoechst 33258 staining,and RT-qPCR were used to detect the cells in vitro.[Results]By screening,key targets of cinnamaldehyde curcumin against liver cancer were obtained,mainly as follows:RAC-α serine/threonine protein kinase(AKT1),epidermal growth factor receptor(EGFR),matrix metalloproteinase-9(MMP9)and tumor necrosis factor(TNF),which involved in 197 pathways including phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)pathway,IL-17 pathway,vascular endothelial growth factor(VEGF)pathway,etc.Molecular docking showed that the combination of the two drugs had a good affinity for AKT1.The key targets of the P13K/Akt pathway were selected and verified in vitro experiments.Cell experiments showed that Compared with the blank control group,cinnamaldehyde combined with curcumin could significantly inhibit the survival rate of SMMC-7721 HCC cells(P＜0.01),significantly increase the apoptosis rate(P＜0.05)and significantly decrease the mRNA expressions of PI3K,AKT1,mTOR,and NF-κB1(P＜0.01).[Conclusion]Curcumin combined with cinnamaldehyde can effectively inhibit the proliferation and induce apoptosis of SMMC-7721 hepatoma cells.Its anti-hepatoma mechanism may be related to the inhibition of the PI3K/Akt signaling pathway.
cinnamaldehydecurcuminnetwork pharmacologyliver cancermechanism of action
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