芒果苷治疗非小细胞肺癌的分子机制研究  

Study on the Molecular Mechanism of Mangiferin in the Treatment of Non-small Cell Lung Cancer

作　　者：元志仁 殷南昌 Yuan Zhiren;Yin Nanchang(The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]锦州医科大学附属第一医院,辽宁锦州121001

出　　处：《南开大学学报（自然科学版）》2023年第2期45-52,共8页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：Supported by the General Project of Liaoning Provincial Department of Education(LJKMZ20221235)。

摘　　要：非小细胞肺癌(NSCLC)是最常见的癌症形式.然而,其机制和治疗策略仍不是很明确.芒果苷(MGF)是一种从芒果叶中提取的黄酮类化合物,具有多种药理和生理作用.本研究旨在阐明芒果苷治疗非小细胞作用机制.网络药理学和分子对接被用于探索MGF治疗NSCLC的潜在分子机制.首先,通过TCMSP,Swiss Target Prediction和Super Pred数据库筛选MGF的作用靶点.然后,从Gene Cards,OMIM,Pharm Gkb,TTD,Drug Bank和Dis Ge NET数据库中获得NSCLC相关的靶点,芒果苷和NSCLC交集靶标由Venny2.1.0获得.通过String数据库和Cytoscape软件绘制了蛋白质-蛋白质相互作用(PPI)网络.接下来,通过Bioconductor平台进行(KEGG)通路富集分析.最后,使用Autodock Vina进行分子对接验证芒果苷和核心靶点的作用关系.结果表明,找到74个MGF潜在靶点,获得了53个芒果苷和NSCLC交集靶点.在PPI网络中,HSP90AA1,ESR1,PTGS2,CXCR4和TLR4确定为核心靶点.KEGG分析表明,MGF治疗NSCLC的主要途径涉及PI3K-Akt,NF-κB和MAPK信号通路.在分子对接中,MGF与核心靶点具有良好的亲和力.最后,MTT实验表明MGF以剂量和时间依赖的方式显著抑制NSCLC细胞(A549,NCI-H460和NCI-H1299细胞)的增殖.综上所述,MGF可通过多靶点和多途径治疗非小细胞肺癌,为进一步研究MGF对非小细胞性肺癌的保护机制和临床应用提供了新思路.Non-small cell lung cancer(NSCLC) is the most prevalent form of lung cancer. However, its mechanism and therapeutic strategy remain to be clarified. Mangiferin(MGF) is a flavonoid derived from the leaves of mango trees that has many pharmacological and physiological effects. The aim of this research is to elucidate the mechanism of MGF in treating NSCLC using network pharmacology, molecular docking, and the biological effect of MGF in NSCLS cell line. The targets of MGF were screened by the TCMSP, Swiss Target Prediction, and Super Pred databases. The targets related to MGF were obtained from the Gene Cards, OMIM,Pharm Gkb, TTD, Drug Bank, and Dis Ge NET databases, and the intersected targets were obtained by Venny2.1.0. The protein-protein interaction(PPI) network was drawn through the String database and Cytoscape software. Next, the pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed by the Bioconductor platform. Finally, molecular docking was conducted using Autodock Vina. The result showed that 74 potential targets of MGF were chosen and 53 overlapping targets were obtained. In the PPI network, HSP90AA1, ESR1, PTGS2, CXCR4, and TLR4 were the core targets. KEGG analyses showed that the main pathways of MGF in treating NSCLC involved PI3K-Akt, NFkappa B, and MAPK signaling pathways. In molecular docking, MGF had a good affinity with the core targets.In vitro experiments, MGF was shown to significantly restrain the proliferation of NSCLC cells(A549, NCIH460, and NCI-H1299 cells) in a dose- and time-dependent manner. In conclusion, MGF can treat non-small cell lung cancer through multiple targets and pathways which could provide new ideas for further research on the protective mechanism and clinical application of MGF against NSCLC.

关 键 词：芒果苷 非小细胞肺癌 网络药理 分子对接 机制 

分 类 号：R932[医药卫生—生药学]