活血祛瘀药对三棱-莪术治疗胃癌的网络药理学作用机制研究

Study on the Mechanism of Sparganii Rhizoma and Curcumae Rhizoma in Treating Gastric Cancer Based on Network Pharmacology

[目的]探讨活血祛瘀药对“三棱-莪术”治疗胃癌(gastric cancer,GC)的有效活性成分及作用机制。[方法]通过中药系统药理学数据库与分析平台(Tradrtional Chinese Medicine systems Pharmacology Database and Analysis Platform,TCMSP)选取三棱-莪术药对中含有的111个化合物,筛选其活性成分及潜在靶点;通过人类孟德尔遗传数据库、Gene Cards数据库挖掘GC疾病靶点;结合化合物及疾病靶点,构建化合物-靶点网络图,并进行基因本体(gene ontology,GO)功能富集及京都基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。[结果]“三棱-莪术”药对中含有60个活性成分,对应GC 67个靶点;主要调控GC细胞的生长增殖周期,包括对细胞核、细胞质、DNA转录、RNA聚合酶Ⅱ启动子等的作用,及对类固醇激素受体活性、丝氨酸型内肽酶活性的调控;发挥作用的重要靶点为半胱天冬氨酸蛋白酶-3(caspase-3,CASP3)、c-Jun N-末端激酶(c-Jun N-terminal kinase,JNK)、雌激素受体1(estrogen receptor 1,ESR1)、热休克蛋白90AA1(heat shock protein90AA1,HSP90AA1)、前列素内环氧化物合成酶2(prostaglandin endoperoxide synthase 2,PTGS2);主要作用的信号通路有肿瘤信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinases-protein kinase B/Akt,PI3K-PKB/Akt)信号通路、p53信号通路、血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、钙信号通路、鞘脂类信号通路等。[结论]中医活血祛瘀之代表“三棱-莪术”药对治疗胃癌作用机制确切,主要通过对细胞周期、靶点蛋白及信号通路的调控发挥其治疗作用。

[Objective]To investigate the active ingredients and mechanisms of Sparganii Rhizoma and Curcumae Rhizoma in treating gastric cancer(GC).[Methods]Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMsp)was used to detect the 111 ingredients in Sparganii Rhizoma and Curcumae Rhizoma.Screening the active ingredients and searching their corresponding targets.Then,disease targets of GC were searched by Online Mendelian Inheritance in Man and Gene Cards database.Compounds and disease targets were combined to construct a compoundtarget network diagram,gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out.[Results]There are 60 active compounds in Sparganii Rhizoma and Curcumae Rhizoma,including 67 targets of GC.GC is mainly treated by regulating cell proliferation cycle,including nuclear,cytoplasm and nucleus DNA transcription,RNA polymeraseⅡpromoter,etc,and the activity of steroid hormone receptor and serine peptidase.Important targets are caspase-3(CASP3),c-jun N-terminal kinase(JNK),estrogen receptor 1(ESR1),heat shock protein 90AA1(HSP90AA1),prostaglandin endoperoxide synthase 2(PTGS2).The main signaling pathways are tumor signaling pathway,phosphatidylinositol 3-kinases-protein kinase B/Akt(PI3K-PKB/Akt)signaling pathway,p53 signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway,tumor necrosis factor(TNF)signaling pathway,calcium signaling pathway,sphingolipid signaling pathway,etc.[Conclusion]As representative of traditional Chinese medicine to promote blood circulation and remove blood stasis,"Sparganii Rhizoma and Curcumae Rhizoma"has an exact mechanism of action in treating GC,mainly through the regulation of cell cycle and signaling pathway.