基于网络药理学和分子对接技术探究青蒿素对宫颈癌的潜在治疗机制及初步验证

Exploration of potential therapeutic mechanisms of artemisinin in cervical cancer based on network pharmacology,molecular docking techniques and initial verification

目的利用网络药理学、分子对接技术和实验研究青蒿素对宫颈癌的潜在治疗机制。方法用Pub Chem、GeneCards数据库获得青蒿素治疗宫颈癌的潜在靶点,并将其导入String数据库、利用Cytoscape3.6.1软件筛选出核心靶点;再利用David数据库进行GO富集分析和KEGG通路分析;用TCMSP、PDB蛋白数据库和Autodock Vina1.1.2软件完成分子对接并计算亲和力;最后用qPCR检测核心基因mRNA表达水平。结果通过数据库分析得到青蒿素治疗宫颈癌的潜在靶点35个,用Cytoscape3.6.1软件筛选出7个核心靶点分别为EGFR、HSP90AA1、MAP2K1、MAPK14、CCNE1、JAK1、PDGFRB,通过GO和KEGG分析,这些靶点可能与EGFR介导的JAK1通路有关。分子对接结果提示青蒿素与核心靶点EGFR、HSP90AA1和JAK1之间可能存在很好的结合作用和匹配度。体外实验验证了青蒿素能抑制EGFR、JAK1基因的转录,这说明与网络药理学预测结果一致,青蒿素对宫颈癌的抑制作用可能与抑制EGFR通路有关。结论本研究阐明了青蒿素治疗宫颈癌的潜在治疗靶点和机制,为宫颈癌临床治疗提供新的思路。

Objective To utilize network pharmacology,molecular docking technology,and experimental research on the potential therapeutic mechanisms of artemisinin on cervical cancer.Methods The PubChem and GeneCards databases to acquire potential targets of artemisinin for treating cervical cancer were obtained,and these targets were imported into the STRING database.Cytoscape 3.6.1 software was employed to filter out core targets.Subsequently,conducted Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis using the DAVID database.Completed molecular docking and calculate binding affinities using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Protein Data Bank(PDB)protein database,and Autodock Vina 1.1.2 software.Lastly,determine the mRNA expression levels of the core genes using quantitative Polymerase Chain Reaction(qPCR).Results Through database analysis,35 potential targets of artemisinin for the treatment of cervical cancer were identified.Using Cytoscape 3.6.1 software,7 core targets were selected:EGFR,HSP90AA1,MAP2K1,MAPK14,CCNE1,JAK1,and PDGFRB.GO and KEGG analysis suggested that these targets might be associated with the EGFR-mediated JAK1 pathway.Molecular docking results indicated that artemisinin may have good binding and compatibility with the core targets EGFR,HSP90AA1,and JAK1.In vitro experiments confirmed that artemisinin can inhibit the transcription of EGFR and JAK1 genes,which is consistent with the predictions from network pharmacology,suggesting that the inhibitory effect of artemisinin on cervical cancer may be related to the inhibition of the EGFR pathway.Conclusions This study elucidated the potential therapeutic targets and mechanisms of artemisinin in the treatment of cervical cancer,providing new insights for clinical treatment of cervical cancer.