Mechanism of icaritin treating multiple myeloma based on networkpharmacology and in vitro experiments
Objective To investigate the mechanism of icaritin in treatment of multiple myeloma through network pharmacology,molecular docking and in vitro experiments.Methods To collect the targets of icaritin using PharmaMapper,SEA,and SwissTargetPrediction databases,and collect disease targets of multiple myeloma using DisGeNET,GeneCards,and MalaCards databases.Using Venn analysis to obtain common targets for action and disease targets,and importing them into the STRING database to analyze the interaction relationships between targets.Then,using Cytoscape software,a visual relationship network between icaritin and potential targets for anti multiple myeloma action is constructed.Then,GO and KEGG enrichment analysis are performed on potential targets,and molecular docking verification is performed on key targets.Further in vitro experiments were conducted on human multiple myeloma U266 cells.The CCK-8 method was used to detect the effect of icaritin on U266 cell proliferation,and qPCR and Western blotting were used to detect the effect of icaritin on the expression of related genes and proteins in key pathways.Results A total of 143 potential targets of icaritin in treatment of multiple myeloma were selected.The important targets were Akt1,ALB,CTNNB1,HSP90AA1,EGFR,MAPK1,ERBB2,and PIK3R1.GO and KEGG enrichment and molecular docking results showed that icaritin may affect the PI3K/Akt signaling pathway.In vitro experiments showed that icaritin could inhibit the proliferation of human multiple myeloma U266 cells,and significantly up-regulate the expression of PIK3R1 and down-regulate the expression of Akt1 in U266 cells(P<0.05,0.01).Conclusion Icaritin could inhibit the proliferation of multiple myeloma cells by regulating the expression of PIK3R1 and Akt1 in the PI3K/Akt signaling pathway,and play a potential role in the treatment of multiple myeloma,providing a theoretical basis for the further development and utilization of icaritin.
icariinmultiple myelomanetworkpharmacologyPI3K/Akt signal pathwaycell proliferation
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