【摘要】 目的:基于生物信息大数据分析,利用网络药理学分析方法,建立冬凌草甲素抗肿瘤的"化合物-靶标-通路-疾病"网络,并探究其潜在的作用机制。方法:借助于PharmMapper服务器寻找冬凌草甲素抗肿瘤的潜在靶蛋白,建立潜在靶蛋白的相互关系网络,通过KEGG数据库对获取的靶点进行相关通路分析,进一步利用Cytoscape软件构建冬凌草甲素的"化合物-靶点-通路-疾病"相互关联网络。结果:数据分析结果表明,冬凌草甲素对人源靶蛋白的105个潜在活性靶点与肿瘤相关。冬凌草甲素抗肿瘤作用于MAP2K1,PIK3R1,TGFβ2,RXRβ,FGFR1,BCL-XL,GSK-3等靶蛋白,其中有19和9个靶蛋白基因分别富集在肿瘤通路、前列腺癌通路和蛋白聚糖肿瘤通路中,有7个靶蛋白基因富集在小细胞肺癌通路中,分别有6个靶蛋白基因富集在结肠直肠癌、胰腺癌和转录失调肿瘤等通路中,主要通过Cytokine-cytokine receptor interaction,PI3K-Akt signaling pathway,PPAR signaling pathway等信号通路起到抗肿瘤的作用。结论:冬凌草甲素有望作为治疗前列腺癌、小细胞肺癌、胰腺癌、结肠直肠癌、甲状腺癌等多种肿瘤的一个新的潜在药物,该研究为冬凌草甲素治疗肿瘤的靶标研究、药理活性与临床应用研究提供了理论支撑。更多还原

【Abstract】 Objective: To establish a "Compound-Target-Pathway-Disease"network,and to explore the possible anticancer mechanism of oridonin,based on big data analytics of biological information and network pharmacology technology. Methods: The possible target proteins of oridonin were searched in PharmMapper,and interactions of the predicted targets were built. The pathway analysis of targets was performed through Kyoto Encyclopedia of Genes and Genomes （KEGG） data base. Furthermore,the network of "Compound-TargetPathway-Disease"was constructed by Cytoscape software. Results: Data analysis showed that oridonin was related to 105 human potential active targets associated with tumors. Theoretically,oridonin might play an anticancer role via MAP2K1,PIK3R1,TGFβ₂,RXRβ,FGFR1,BCL-XL,GSK-3 and other target proteins. Among them,19 and 9 target genes are enriched in cancer proteoglycans and prostate cancer,7 in small cell lung cancer,6 in colorectal cancer,pancreatic cancer,transcriptional misregulation,respectively. The anticancer effects could be associated with cytokine-cytokine receptor interaction,PI3K-Akt signaling pathway,and PPAR signaling pathway.Conclusion: Oridonin may be considered as a new potential and promising drug for the treatment of some cancers such as prostate cancer,small cell lung cancer,pancreatic cancer,colorectal cancer,and thyroid cancer. We suggest a possibility for researching the anticancer effects of oridonin in the aspects of targeting,pharmacological activity,and clinical application.更多还原