基于网络药理学及分子对接探讨荜茇治疗胃癌的作用机制研究

doi:10.19803/j.1672-8629.20220655

摘要/Abstract

摘要： 目的采用网络药理学及分子对接技术探究荜茇治疗胃癌的作用机制。方法在中药系统药理学分析平台（TCMSP）检索荜茇成分及活性成分;利用GeneCards数据库检索与胃癌相关靶点及共同基因;绘制PPI网络图,分别进行GO和KEGG富集分析;利用AutoDock Tools1.5.6软件对核心成分及靶点进行分子对接。MTT、流式细胞术检测不同浓度胡椒碱对SGC-7901细胞抑制及细胞凋亡的影响;蛋白免疫印迹法检测相关蛋白表达水平。结果检索到荜茇活性成分15个;荜茇-胃癌共同靶点15个;GO功能富集分析关联到基因生物过程19条,细胞组成12条,分子功能4条,KEGG通路富集分析主要涉及TNF信号通路等;分子对接结果显示胡椒碱、芝麻素等与核心靶点分子对接结果良好。MTT法及流式细胞术结果显示,与对照组相比,胡椒碱组SGC-7901细胞抑制率增加（P<0.01）,细胞凋亡率增加（P<0.01）;Western blotting结果显示,与对照组相比,胡椒碱组SGC-7901细胞中TNF-α、Caspase-3、Caspase-8蛋白表达量增加（P<0.05）。结论荜茇及活性成分胡椒碱对胃癌的治疗呈多靶点、多通路的特征,可为后续实验研究和临床应用提供参考。

关键词: 胃癌, 荜茇, 胡椒碱, 网络药理学, 分子对接, MTT法, 流式细胞术, 蛋白免疫印迹法

Abstract: Objective To explore the mechanism of Piper longum for the treatment of gastric cancer via network pharmacology and molecular docking technology. Methods The components and active components of Piper longum were searched for in TCMSP. GeneCards database was used to search for targets and common genes related to gastric cancer. A PPI network diagram was drawn, and GO and KEGG enrichment analysis was performed respectively. AutoDock Tools1.5.6 software was used for molecular docking of core components and targets. MTT and flow cytometry were used to detect the effects of different concentrations of piperine on the inhibition and apoptosis of SGC-7901 cells. The expression levels of related proteins were detected by Western blotting. Results A total of 15 active components were identified. There were 15 common targets of Piper longum-gastric cancer. GO functional enrichment analysis was associated with 19 gene biological processes, 12 cell components and 4 molecular functions. KEGG pathway enrichment analysis mainly involved the TNF signaling pathway. Molecular docking results of piperine, sesamin and other core targets were good. The results of MTT assay and flow cytometry showed that compared with the control group, the inhibition rate of SGC-7901 cells in the piperine group was increased ( P < 0.01 ), so was the apoptosis rate ( P < 0.01 ). Western blotting results showed that compared with the control group; the expressions of TNF-α, Caspase-3 and Caspase-8 protein in SGC-7901 cells in the piperine group increased (P < 0.05). Conclusion Piper longum and piperine have multi-target and multi-pathway properties in the treatment of gastric cancer, which can provide reference for subsequent experimental research and clinical application.

Key words: gastric cancer, Piper longum, piperine, network pharmacology, molecular docking, MTT, flow cytometry, western blotting

中图分类号:

王如梦, 郭梓琪, 杨宏新, 杨勇. 基于网络药理学及分子对接探讨荜茇治疗胃癌的作用机制研究[J]. 中国药物警戒, 2023, 20(10): 1121-1128.

WANG Rumeng, GUO Ziqi, YANG Hongxin, YANG Yong. Mechanisms of Piper longum for treating gastric cancer based on network pharmacology and molecular docking[J]. Chinese Journal of Pharmacovigilance, 2023, 20(10): 1121-1128.

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