基于网络药理学和分子对接探讨通关藤治疗胃癌的作用机制

Mechanisms of Marsdenia tenacissima in inhibiting gastric cancer based on network pharmacology and molecular docking technology

目的基于网络药理学技术分析和分子对接探讨通关藤抗胃癌的作用机制。方法采用PubMed数据库检索文献,利用化学成分数据库及Swiss ADME筛选通关藤的主要活性成分,通过Swiss Target Prediction获取药物活性成分靶点。检索疾病数据库得到胃癌相关靶点,与药物活性成分靶点取交集后,制作蛋白质-蛋白质相互作用(PPI)网络图,筛选通关藤作用于胃癌的关键靶点蛋白。采用AutoDock及PyMOL对关键蛋白进行分子对接验证,采用DAVID数据库进行关键蛋白富集分析,结合两者结果预测通关藤可能的分子作用机制。结果筛选后共得到通关藤有效活性成分36个,作用于胃癌的靶点116个,预测通路与ErbB、VEGF、EGFR、PI3K/Akt等相关。结论通关藤可能通过影响SRC、PTK2、HSP90AA1等关键蛋白调节PI3K/Akt、Ras/Raf/MEK/ERK、SRC/FAK等相关信号转导通路,从而抑制胃癌的侵袭与转移,起到治疗胃癌的作用。

Objective To explore the mechanisms of Marsdenia tenacissima in inhibiting gastric cancer based on network pharmacology and molecular docking technology. Methods PubMed database was used to search the literatures, and main active ingredients of Marsdenia tenacissima were screened by Chemical Composition Database and Swiss ADME. The core targets related to Marsdenia tenacissima were screened by retrieving disease databases, and protein-protein interaction(PPI) network map based on common target of active ingredients and gastric cancer was constructed by network pharmacology. AutoDock and PyMOL were used to perform molecular docking verification of active ingredients with key targets. DAVID database was used to perform enrichment analysis of key proteins. The molecular mechanism of Marsdenia tenacissima in inhibiting gastric cancer was predicted by their combined results. Results Marsdenia tenacissima in inhibiting gastric cancer had thirty-six effective active components, acting on 116 target proteins. It was predicted that the pathways were related ErbB, VEGF, EGFR, PI3 K/Akt, etc. Conclusion Marsdenia tenacissima inhibits the invasion and metastasis of gastric cancer through the regulation of the key proteins such as SRC, PTK2 and HSP90 AA1. The molecular mechanisms may be associated with PI3 K/Akt, Ras/Raf/MEK/ERK or SRC/FAK signaling pathways,thereby treating gastric cancer.