Exploring mechanism of action and experimental validation of chrysotoxine against cervical cancer based on network pharmacology and molecular docking
Objective To investigate the mechanism of chrysotoxine in the treatment of cervical cancer using network pharmacology and molecular docking and validate the results through cell-based experiments.Methods Predicted targets of chrysotoxine were obtained by TCMSP,PharmMaper and SwissTarget Prediction platform.The potential targets of cervical cancer were screened in GeneCards,TTD,OMIM,Disgenet and Drugbank disease databases.R software Venn package was used to obtain common target genes of chrysotoxine and cervical cancer.STRING website and Cytoscape software were used to obtain the PPI network,screened the core targets,and analyzed them for GO and KEGG enrichment.Molecular docking and visualization between chrysotoxine and the core targets were conducted using Autodock Vina 1.1.2 and Pymol software.Cervical cancer cells SiHa were cultured and treated with 0,50,100 pmol·L-1 chrysotoxine in vitro,and the effects of chrysotoxine on cell proliferation,migration and invasion were detected by MTT assay and Transwell assay,respectively.The molecular mechanism of chrysotoxine against cervical cancer was performed by Western blotting,focusing on the regulatory proteins of p-PI3K,PI3K,p-Akt,Akt,and mTOR in the PI3K/Akt/mTOR signaling pathway.Results A total of 79 potential common targets of chrysotoxine against cervical cancer were obtained,and then screened multiple core targets according to the degree value,such as:HSP90AA1,ESR1,PIK3CA,mTOR,MAPK1,ABL1,PARP1,et al.KEGG enrichment screened 30 pathways,including PI3K/Akt signaling pathway,Focal adhesion signaling pathway,cellular senescence signaling pathway,prolactin signaling pathway,et al.Molecular docking results showed that chrysotoxine had a higher affinity for target proteins,such as HSP90AA1,ESR1,PIK3CA,mTOR,and MAPK1,suggesting their potential role in chrysotoxine's anti-cervical cancer effects.Cellular experiments demonstrated that chrysotoxine significantly reduced the proliferation of SiHa cells(P＜0.01)and decreased their migration and invasion ability.Western blotting results further confirmed the down-regulation(P＜0.05)of p-PI3K,Akt,p-Akt,p-PI3K/PI3K,and p-Akt/Akt expression after treatment with chrysotoxine.Conclusion Chrysotoxine can exert therapeutic effects on cervical cancer through multi-targets and multi-pathways,and chrysotoxine may affect the proliferation and migration of cervical cancer cells by inhibiting the expression of PI3K/Akt/mTOR signaling pathway.These provide a reliable theoretical basis for the treatment of cervical cancer with chrysotoxine,and provide a new idea for the traditional Chinese medicine treatment of cervical cancer in the future.
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