| 引用本文: |
涂雅玲, 陈其华, 席建元, 祁林, 赵多多, 喻环宇.基于网络药理学探讨扶正解毒抗癌汤治疗黑色素瘤的作用机制[J].湖南中医药大学学报,2025,45(1):39-48[点击复制] |
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| 基于网络药理学探讨扶正解毒抗癌汤治疗黑色素瘤的作用机制 |
| 涂雅玲,陈其华,席建元,祁林,赵多多,喻环宇 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨扶正解毒抗癌汤（FZJDD）治疗黑色素瘤的分子机制。方法 TCMSP和TCMID的数据库和文献中检索FZJDD有效化学成分及各成分对应的作用靶点；GeneCards、OMIM、TTD等数据查询库中筛选黑色素瘤相关靶点，获得“药物-疾病”交集靶点，STRING 11.5与DAVID数据库进行蛋白质-蛋白质相互作用（PPI）网络分析获取核心靶点，Cytoscape 3.8.1构建FZJDD治疗黑色素瘤中药-作用靶标-通路网络，GO富集分析与KEGG富集分析获取FZJDD治疗黑色素瘤的关键生物学过程及信号通路。借助qPCR及Western blot方法验证相关信号通路关键蛋白的作用。结果 获得FZJDD有效成分47个，“药物-疾病”交集靶点168个，富集到的信号通路主要包括磷脂酰肌醇三激酶（PI3K）/蛋白激酶B(AKT)等信号通路；体外细胞实验显示，FZJDD能够有效降低黑色素瘤A375细胞增殖，抑制PI3K/AKT信号通路关键蛋白PI3K、AKT、雷帕霉素靶蛋白（mTOR）的蛋白及mRNA表达水平（P<0.05）。结论 FZJDD可以通过多成分、多靶点、多通路，发挥抗炎、促进肿瘤细胞凋亡等作用治疗黑色素瘤，其中对PI3K/AKT通路的调控可能是其关键机制。 |
| 关键词: 扶正解毒抗癌汤 黑色素瘤 PI3K/AKT信号通路 网络药理学 作用机制 |
| DOI：10.3969/j.issn.1674-070X.2025.01.006 |
| 投稿时间：2024-08-31 |
| 基金项目:湖南省研究生科研创新重点项目(CX20210680);湖南省教育厅科学研究重点项目(21A0224);湖南省教育厅科学研究优秀青年项目(23B0377);湖南省中医药管理局中医药科研课题(C2024012);2024年湖南省大学生创新训练计划项目(S202410541030);湖南中医药大学校院联合基金重点项目(2023XYLH002)。 |
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| Mechanism of action of Fuzheng Jiedu Kang’ai Decoction in treating melanoma based on network pharmacology |
| TU Yaling, CHEN Qihua, XI Jianyuan, QI Lin, ZHAO Duoduo, YU Huanyu |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To explore the molecular mechanism of Fuzheng Jiedu Kang’ai Decoction（FZJDD） in the treatment of melanoma. Methods The effective chemical components of FZJDD and their corresponding targets were retrieved from the databases and literature of TCMSP and TCMID. Melanoma-related targets were screened using databases such as GeneCard,OMIM, and TTD to obtain intersection targets of "drug-disease". Protein-protein interaction（PPI） network analysis was performed using STRING11.5 and DAVID databases to identify core targets. Cytoscape 3.8.1 was used to construct a Chinese medicinesaction targets-pathway networks for FZJDD in treating melanoma. Gene ontology function（GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were conducted to identify the key biological processes and signaling pathways involved in treating melanoma with FZJDD. Quantitative real-time PCR（qPCR） and Western blot were used to validate the roles of key proteins in related signaling pathways. Results A total of 47 active components of FZJDD and 168 "drugdisease" intersection targets were identified. The enriched sign aling pathways mainly included phosphatidylinositol 3-kinase（PI3K）/protein kinase B（AKT） signaling pathway, among others. In vitro cell experiments showed that FZJDD effectively inhibited the proliferation of melanoma A375 cells and suppressed the protein and mRNA expression levels of key proteins in PI3K/AKT signaling pathway, including PI3K, AKT, and the mammalian target of rapamycin（mTOR）（P＜0.05）. Conclusion FZJDD can treat melanoma by exerting anti-inflammatory effects and promoting tumor cell apoptosis through multiple components, targets,and pathways, among which the regulation of the PI3K/AKT pathway may be its key mechanism. |
| Key words: Fuzheng Jiedu Kang’ai Decoction melanoma PI3K/AKT signaling pathway network pharmacology mechanism of action |
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