| 引用本文: |
刘艳霞, 顾展丞, 杨华, 陆琼, 钱丽君, 杨文娟, 曹宏.基于网络药理学的小泻肺汤抗肺腺癌机制研究及动物实验验证[J].湖南中医药大学学报,2025,45(6):1149-1155[点击复制] |
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| 基于网络药理学的小泻肺汤抗肺腺癌机制研究及动物实验验证 |
| 刘艳霞,顾展丞,杨华,陆琼,钱丽君,杨文娟,曹宏 |
| (昆山市中医医院, 江苏 苏州 215300) |
| 摘要: |
| 目的 基于网络药理学探讨小泻肺汤（XXFD）治疗肺腺癌的靶点和作用机制，并进行体内实验验证。方法 从TCMSP和UniProt数据库及文献中检索XXFD有效化学成分及各成分相应的作用靶点；从GeneCards、OMIM等数据库筛选肺腺癌相关靶点，用Venny 2.1.0在线工具获得药物和疾病的交集靶点，作为XXFD治疗肺腺癌的潜在靶点；利用STRING数据库和Cytoscape 3.9.1软件构建蛋白质-蛋白质相互作用（PPI）网络，并获取核心靶点；通过DAVID数据库对交集靶点进行GO功能富集分析和KEGG通路富集分析；利用Cytoscape 3.9.1软件构建XXFD治疗肺腺癌的成分-靶点-信号通路网络图。建立裸鼠皮下移植瘤模型，随机分为空白对照组和XXFD组（生药量为1.8 g/20 g），每组5只。每日观察小鼠的整体情况，每隔3日测量并记录裸鼠瘤体体积。给药3周后处死小鼠，迅速剥离肿瘤组织并用电子天平称重，Western blot法检测肿瘤组织中肿瘤蛋白53（TP53）、蛋白激酶B（Akt）、原癌基因（JUN）、肿瘤坏死因子（TNF）、热休克蛋白90α（HSP90AA1）的蛋白表达水平。结果 网络药理学分析表明，XXFD有118个潜在靶点，后续筛选得到度值排名前5的核心靶点，分别为TP53、Akt、JUN、TNF、HSP90AA1。GO功能富集分析显示，XXFD治疗肺腺癌的靶基因主要作用于基因调控、酶结合等过程。KEGG通路富集分析显示，XXFD治疗肺腺癌主要涉及癌症信号通路、TNF信号通路、白细胞介素-17（IL-17）信号通路及凋亡信号通路等多条信号通路。动物实验验证结果显示，与空白对照组比较，XXFD组显著抑制裸鼠皮下移植瘤的生长（P<0.05），减轻瘤体体积和质量（P<0.05），显著促进瘤体组织中P53蛋白表达（P<0.05），抑制TNF-α、p-Akt、c-JUN、HSP90蛋白表达（P<0.05）。结论 XXFD可能通过多途径、多靶点抑制肿瘤生长，实现其在肺腺癌治疗中的作用。 |
| 关键词: 肺腺癌 小泻肺汤 网络药理学 肿瘤蛋白53 蛋白激酶B 原癌基因 肿瘤坏死因子 热休克蛋白90α |
| DOI：10.3969/j.issn.1674-070X.2025.06.026 |
| 投稿时间：2024-10-11 |
| 基金项目:江苏省中医药科技发展计划项目（QN202324）；昆山市重点研发计划项目（KS2432）。 |
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| Mechanism of Xiao Xiefei Decoction on lung adenocarcinoma based on network pharmacology and in vitro experimental validation |
| LIU Yanxia, GU Zhancheng, YANG Hua, LU Qiong, QIAN Lijun, YANG Wenjuan, CAO Hong |
| (Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu 215300, China) |
| Abstract: |
| Objective To explore the potential targets and mechanisms of Xiao Xiefei Decoction (XXFD) in the treatment of lung adenocarcinoma based on network pharmacology, followed by in vivo experimental validation.Methods Effective chemical components of XXFD and their corresponding targets were obtained from TCMSP and UniProt databases, as well as literature sources. Lung adenocarcinoma-related targets were identified using the GeneCards and OMIM databases. Venny 2.1.0 was used to determine the overlapping targets between the drug and the disease, representing the potential targets of XXFD in treating lung adenocarcinoma. A protein-protein interaction (PPI) network was constructed using STRING database and Cytoscape 3.9.1 software to identify key targets. GO functional and KEGG enrichment analyses of the intersecting targets were performed using DAVID database. A component-target-pathway network of XXFD in the treatment of lung adenocarcinoma was constructed using Cytoscape 3.9.1 software. An in vivo subcutaneous xenograft tumor model was established in nude mice, which were randomly divided into a blank control group and an XXFD-treated group (crude drug dose of 1.8 g/20 g), with 5 mice in each group. The overall condition of mice was observed daily, and the tumor volume of nude mice was measured and recorded every 3 days. After 3 weeks of administration, the mice were sacrificed, the tumor tissues were rapidly peeled off and weighed with an electronic balance. Western blot was used to check the protein expression levels of tumor protein 53 (TP53), protein kinase B (AKT), proto-oncogene (JUN), tumor necrosis factor (TNF), and heat shock protein 90α (HSP90AA1) in tumor tissues.Results Network pharmacology analysis identified 118 potential targets of XXFD, and the top 5 core targets based on degree value were TP53, AKT, JUN, TNF, and HSP90AA1. GO functional enrichment analysis showed that these target genes of XXFD treatment for lung adenocarcinoma mainly acted on gene regulation and enzyme binding. KEGG pathway enrichment analysis suggested that the anti-lung adenocarcinoma effects of XXFD are related to multiple signaling pathways, including cancer, TNF, interleukin-17 (IL-17), and apoptosis signaling pathways. In vivo animal experiments showed that compared with the control group, the XXFD group significantly inhibited the growth of subcutaneous xenograft tumors in nude mice (P<0.05), reduced the tumor volume and weight (P<0.05), significantly upregulated the expression of P53 protein in tumor tissues (P<0.05), and downregulated the protein expression levels of TNF-α, p-AKT, c-JUN, and HSP90 (P<0.05).Conclusion XXFD may exert its therapeutic effects on lung adenocarcinoma by inhibiting tumor growth through multiple pathways and targets. |
| Key words: lung adenocarcinoma Xiao Xiefei Decoction network pharmacology tumor protein 53 protein kinase B proto-oncogene tumor necrosis factor heat shock protein 90α |
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