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娄余,朱莹,彭瑶,王燚霈,易书林.基于网络药理学探讨三物白散治疗胃癌的分子机制及初步验证[J].湖南中医药大学学报英文版,2021,41(4):566-575.[Click to copy
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| 基于网络药理学探讨三物白散治疗胃癌的分子机制及初步验证 |
| 娄余,朱莹,彭瑶,王燚霈,易书林 |
| (湖南中医药大学第二附属医院, 湖南 长沙 410005;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 运用网络药理学联合分子对接探讨三物白散治疗胃癌的作用机制，通过体外细胞实验对相关靶点作初步验证。方法 利用TCMSP数据库获取三物白散的活性成分及潜在靶点；通过Genecards、OMIM、TTD数据库，收集胃癌相关的作用靶点；将三物白散潜在靶点与胃癌靶点相匹配，获得三物白散抗胃癌的作用靶点，使用STRING数据库对作用靶点进行蛋白互作分析，构建PPI网络，并进行拓扑分析筛选核心靶点；用R语言对作用靶点进行GO生物学过程和KEGG通路富集分析；采用Auto Dock Vina软件对核心靶点与对应活性成分进行分子对接；运用qPCR验证三物白散对胃癌细胞SGC-7901中Caspase-3、Caspase-7作用靶点的调控作用。结果 经筛选获得三物白散活性成分17个，三物白散作用靶点84个，经拓扑分析得到12个核心作用靶点，包括TP53、AKT1、MAPK1、JUN、CASP3等。三物白散作用靶点涉及PI3K-AKT、p53、HIF-1、IL-17等多条信号通路，通过诱导细胞凋亡、抑制细胞增殖、调节缺氧及炎性微环境发挥抗肿瘤作用。分子对接结果表明，活性成分与核心靶点有良好的结合能力。体外实验结果证实，三物白散可上调凋亡相关分子Caspase-3、Caspase-7的表达，这在一定程度上证实了网络药理学预测及指导实验设计的可靠性。结论 本研究结果体现了三物白散多成分、多靶点、多通路的治疗特点，系统地揭示了其抗胃癌的药效物质、核心靶点和信号通路，为后续深入研究作用机制提供参考。 |
| 关键词: 胃癌 三物白散 网络药理学 作用靶点 分子对接 体外细胞实验 |
| DOI：10.3969/j.issn.1674-070X.2021.04.013 |
| Received:August 18, 2020 |
| 基金项目:中医内科重大疾病防治研究与转化教育部重点实验室开放基金（ZYNK201705）；湖南省研究生科研创新项目（CX20190546）。 |
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| Molecular Mechanism of Sanwubai Powder in Treatment of Gastric Cancer Based on Network Pharmacology and Preliminary Validation |
| LOU Yu,ZHU Ying,PENG Yao,WANG Yipei,YI Shulin |
| (The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China;The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To investigate the mechanism of Sanwubai Powder in the treatment of gastric cancer based on network pharmacology combined with molecular docking, and to preliminarily verify the related targets by in vitro cell experiments. Methods TCMSP was used to screen and predict the compounds and targets in Sanwubai Powder. Targets related to gastric cancer were collected by GeneCards, OMIM and TTD databases. The potential targets of Sanwubai Powder were matched with the targets of gastric cancer to obtain the anti-gastric cancer targets of Sanwubai Powder, STRING was used to analyze the protein-protein interaction of targets, PPI network was structured and then the core targets were screened by using topology analysis. GO biological process analysis and KEGG pathway enrichment analysis were performed by R language. Auto Dock Vina software was used to dock the core targets with the active ingredients. qPCR was used to verify the regulatory effects of Sanwubai Powder on the targets of Caspase-3 and Caspase-7 in gastric cancer cells SGC-7901. Results 17 active components were screened, and 12 hub targets of 84 targets including TP53, AKT1, MAPK1, JUN and CASP3 were obtained of Sanwubai Powder. The targets of Sanwubai Powder involved PI3K-Akt, p53, HIF-1, IL-17 signal pathways, which played an anti-tumor role by inducing cell apoptosis, inhibiting cell proliferation, regulating hypoxia and inflammatory microenvironment. The results of molecular docking showed that active ingredients had good binding capacity with targets. The results of in vitro experiments confirm that, Sanwubai Powder could up-regulate the expression of apoptosis-related molecules Caspase-3 and Caspase-7, which to a certain extent confirmed the reliability of network pharmacological prediction and experimental design guidance. Conclusion The results of this study reflected the therapeutic characteristics of Sanwubai Powder with multiple components, multiple targets and multiple pathways, revealed the active components, key targets and important pathways of Sanwubai Powder in the treatment of gastric cancer, and provided research ideas and reference basis for further discussion on the mechanism of action. |
| Key words: gastric cancer Sanwubai Powder network pharmacology effect target molecular docking in vitro cell experiment |
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