中国药理学通报2025，Vol.41Issue(7)：1367-1375,9.DOI:10.12360/CPB202411045
基于网络药理学和体外实验验证探讨高车前素抗宫颈癌的作用机制
Mechanism of action of hispidulin on cervical cancer based on network pharmacology and in vitro cell experiments
摘要
Abstract
Aim To explore the mechanism of hispidu-lin in the treatment of cervical cancer by using network pharmacology and molecular docking methods and veri-fy it by in vitro experiments.Methods Cervical canc-er HeLa and SiHa cells were cultivated in vitro,and CCK-8 assay,cloning assay,scratch assay,transwell as-say,and flow cytometry were used to detect the effects of hispidulin on cell proliferation,migration,invasion,and apoptosis.SwissTarget Prediction was used to ob-tain predicted targets for hispidulin.Potential targets for cervical cancer were screened in GeneCards disease database.R software Venn package was used to obtain the intersection target genes of hispidulin and cervical cancer,STRING website and Cytoscape software were used to obtain protein-protein interaction(PPI)net-work,and the core targets were screened.The GEIPA data analysis platform was employed to analyze the dif-ferential gene expression levels of core targets in cervi-cal cancer.Gene Ontology(GO)and Kyoto Encyclo-pedia of Genes and Genomes(KEGG)enrichment a-nalysis were performed,and molecular docking was car-ried out on key targets.Western blot was used to detect the regulatory effects of hispidulin on the expression of key proteins PI3K,p-Akt,as well as core target pro-teins MMP9 and RARP1 in the PI3K/Akt signaling pathway.Results Cell experiments showed that after treatment with hispidulin,the proliferation and colony formation abilities of HeLa and SiHa cells significantly decreased in a concentration-and time-dependent man-ner.At the same time,the lateral and longitudinal mi-gration and invasion abilities of HeLa cells decreased,and the level of apoptosis significantly increased.A to-tal of 87 intersection targets between hispidulin and cervical cancer were obtained,and eight core targets,namely,Akt1,EGFR,SRC,ESR1,PTGS2,GSK3β,MMP9,and PARP1,were selected based on the degree values in network topology analysis.KEGG enrichment screening identified PI3K/Akt signaling pathway,canc-er pathway,and other signaling pathways.The molecu-lar docking results showed that hispidulin had strong affinity activity with AktⅠ,P13K,MMP9,and RARP1.Western blot results showed downregulation of PI3K,p-Akt expression,as well as MMP9 and RARP1 expres-sion.Conclusions Hispidulin can inhibit the prolif-eration,migration,invasion,and promote apoptosis of cervical cancer cells by downregulating the PI3K/Akt signaling pathway and the expression of MMP9 and RARP1.关键词
高车前素/宫颈癌/网络药理学/分子对接/PI3K/Akt信号通路/作用机制Key words
hispidulin/cervical cancer/network phar-macology/molecular docking/PI3K/Akt signaling pathway/mechanism of action分类
中医学引用本文复制引用
孟慧君,黄文洁,于肖童,杨海,王晔..基于网络药理学和体外实验验证探讨高车前素抗宫颈癌的作用机制[J].中国药理学通报,2025,41(7):1367-1375,9.基金项目
山东省自然科学基金(No ZR2024MH291) （No ZR2024MH291）
国家自然科学基金资助项目(No 82072927) （No 82072927）
