摘要
目的:应用网络药理学方法探讨白术、莪术药对抗肿瘤作用机制,并分析潜在作用靶点的临床意义。方法:使用公共数据库分别收集白术、莪术药对的作用靶点和肿瘤疾病的靶点,取交集获得药物抗肿瘤作用的潜在靶点,基于抗肿瘤靶点预测相关转录因子、构建蛋白互作网络和药物成分-靶点网络,应用通路富集分析方法探索作用通路和途径,利用分子对接分析药物成分与靶点蛋白的结合潜能,基于TIMER数据库分析抗肿瘤靶点与免疫细胞浸润的关系,从TCGA获取抗肿瘤靶点在肿瘤组织中的表达情况并分析其对患者临床预后的影响。结果:获得白术、莪术药对抗肿瘤的潜在靶点379个,包括AKT1、VEGFA、GRM3、GRM4等核心靶点,以及STAT3、TP53等相关转录因子。作用机制主要涉及凋亡、炎症反应、缺氧应答、谷氨酸受体信号通路、cAMP信号通路、Rap1信号通路、雌激素信号通路、HIF-1信号通路、VEGF信号通路等,且核心靶点AKT1、VEGFA、GRM3的表达水平对乳腺浸润癌、结肠腺癌、肝细胞肝癌等肿瘤患者的临床预后有不同程度的贡献。结论:白术、莪术药对可以通过多靶点、多途径发挥抗肿瘤作用,为进一步药理研究提供了思路和线索。
Objective:To explore the antitumor mechanism of Baizhu(Atractylodes macrocephala)-Ezhu(Curcuma zedoaria) by using the method of network pharmacology,and to analyze the clinical significance of potential antitumor targets.Methods:The public databases were used to collect the targets of Baizhu(Atractylodes macrocephala)-Ezhu(Curcuma zedoaria) and the targets of tumor diseases.The potential targets of antitumor effects of drugs were obtained by intersection.Based on the antitumor targets,the related transcription factors were predicted,the protein interaction network and the drug composition-target network were constructed.Enrichment analysis was used to explore the pathways and pathways.Molecular docking was used to analyze the binding potential of drug components and target proteins.The relationship between antitumor targets and immune cell infiltration was analyzed based on the TIMER database.The expression of antitumor targets in tumor tissues was obtained from TCGA and its influence on the clinical prognosis of patients was analyzed.Results:379 potential antitumor targets of Baizhu(Atractylodes macrocephala)-Ezhu(Curcuma zedoaria) were obtained,including core targets such as AKT1,VEGFA,GRM3,GRM4,and related transcription factors such as STAT3 and TP53.The mechanism of action mainly involves apoptosis,inflammatory response,hypoxia response,glutamate receptor signaling pathway,c AMP signaling pathway,Rap1 signaling pathway,estrogen signaling pathway,HIF-1 signaling pathway,VEGF signaling pathway,and the expression levels of core targets AKT1,VEGFA,GRM3 have different degrees of contribution to the clinical prognosis of patients with invasive breast cancer,colon adenocarcinoma,hepatocellular carcinoma and other tumors.Conclusion:Baizhu(Atractylodes macrocephala)-Ezhu(Curcuma zedoaria) can exert antitumor effects through multiple targets and multiple pathways,which provides ideas and clues for further research.
作者
汪猛
邱文超
秦凯健
WANG Meng;QIU Wenchao;QIN Kaijian(Shanghai Fourth People's Hospital Affiliated to Tongji University,Shanghai 200434,China;Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)
出处
《中医药导报》
2022年第8期45-54,75,共11页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
上海市虹口区“国医强优”三年行动计划(HGY-KY-2018-01)
上海市虹口区卫生健康委员会中医药科研课题(HKQ-ZYY-202047)。
关键词
抗肿瘤
白术
莪术
药对
网络药理学
临床意义
antitumor
Baizhu(Atractylodes macrocephala)
Ezhu(Curcuma zedoaria)
drug pair
network pharmacology
clinical significance
