利用网络药理学与分子对接技术分析石见穿在治疗癌症中的作用机制  

Study on the Mechanism of Salviae Chinensis Herba in Treating Cancer Based on Network Pharmacology and Molecular Docking Technology

作　　者：刘利艳[1,2] 施旻 陈力[4] 张洁 李斌 温世伟[4] 徐彭 LIU Liyan;SHI Min;CHEN Li(Jiangxi Cancer Hospital,Nanchang,330029)

机构地区：[1]江西省肿瘤医院,南昌大学附属肿瘤医院,330029 [2]江西中医药大学实验动物科技中心,330004 [3]江西中医药大学中医学院,330004 [4]成都中医药大学药学院,610500 [5]江西中医药大学院士工作站,330004

出　　处：《实用癌症杂志》2021年第10期1572-1576,共5页The Practical Journal of Cancer

基　　金：江西省卫生计生委中医药科研课题(编号:2014A026,2018A310);江西省卫生健康委员会科技计划(编号:202130722);中央本级重大增减支项目(编号:2060302);江西中医药大学院士工作站项目(编号:YSGZZ201801);江西中医药大学一流学科项目(编号:JXSYLXK-ZHYAO144)。

摘　　要：目的利用网络药理学和分子对接技术分析石见穿治疗癌症的作用机制。方法分别基于不同数据库收集石见穿的所有活性成分,寻找活性成分的预测靶点,获得所有癌症相关基因,再通过String结合Cytoscape绘制蛋白相互作用网络,归纳总结石见穿主要潜在靶点,采用DISCOVERY STUDIO对接潜在的作用靶点(靶点数目最多的活性成分和蛋白相互作用中自由度最大的蛋白质)。结果石见穿主要的活性成分为阿魏醛、熊果酸和齐墩果酸等,预测靶点与癌症交叉共有靶点有84个,核心靶点分别为白介素-6(IL-6)、丝裂原活化蛋白激酶1和3(MAPK1、MAPK3)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)、前列腺素内过氧化物合酶2(PTGS2),分子对接显示石见穿中阿魏醛能与IL-6稳定结合,并分别通过氨基酸残基SER L52、ARG H99、ARG H33、ALA H100、GLY L36、ASP L93、ASP H106;齐墩果酸能与MAPK3、EGFR稳定结合,分别通过GLU B50、ALA A289、SERA291、THR A339、VAL A312、CYS A309、CYS A305、ARG A310等氨基酸残基连接。熊果酸分别通过GLY B49、VAL B56、TYRB53、LEUB124、ILEB48、CYSB183、METB125、LEUB173等氨基酸残基与MAPK3、EGFR稳定结合。结论该研究揭示了石见穿治疗癌症是基于多成分、多靶点、多通路的协作相互作用的潜在机制,为后续的分子机制研究提供方向与思路。Objective To construct a network of"compound-target-disease-pathway"for the treatment of cancer by using network pharmacology and molecular docking techniques to explore the mechanism of anti-tumor effect of Salviae Chinensis Herba.Methods All ingredients of Salviae Chinensis Herba were collected,the predicted targets of active components were searched,the disease targets were collected from different database,and the main potential targets of Salviae Chinensis Herba were summarized by combining the String network platform with Cytoscape software,and the molecular docking software DISCOVERY STUDIO was used to validate the potential target(the active component with the highest number of targets and the most frequency in protein interaction).Results The main active components may be ferulicaldehyde,ursolic acid and oleanolic acid and there were 84 common targets for the cross-predicted target and cancer cross-section.The core target is interleukin-6(IL-6).Mitogen-activated protein kinases 1 and 3(MAPK1,MAPK3),epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),prostaglandin endoperoxide synthase 2(PTGS2),etc.Molecular docking showed that the ferulicacetaldehyde could stably bind toIL-6 which passed the amino acid residues SER L52,ARG H99,ARG H33,ALA H100,GLY L36,ASP L93,ASP H106 respectively.Oleanolic acid can stably bind to MAPK3 and EGFR,which pass through amino acid residues such as GLU B50,ALA A289,SER A291,THR A339,VAL A312,CYS A309,CYS A305,ARG A310.Ursolic acid is stably bound to MAPK3 and EGFR by amino acid residues such as GLY B49,VAL B56,TYRB53,LEUB124,ILEB48,CYSB183,MET B125 and LEUB173 respectively.Conclusion The treatment of cancer by Salviae Chinensis Herba is based on the potential mechanism of multi-component,multi-target,multi-channel collaborative interaction,providing direction and ideas for subsequent research.

关 键 词：网络药理学 分子对接 石见穿 癌症 分子机制 

分 类 号：R73-36[医药卫生—肿瘤]