目的 基于网络药理学、分子对接技术和体外实验验证探究五味子丙素抗胶质瘤的作用及其机制。方法 通过TCMSP等数据库筛选五味子丙素相关靶点，借助GeneCards等数据库收集胶质瘤相关靶点，得到五味子丙素与胶质瘤的交集靶点并绘制韦恩图，用STRING数据库构建PPI网络，并利用Cytoscape软件筛选出核心交集靶点。利用DAVID数据库对交集靶点进行基因本体论（GO）和京都基因和基因百科全书（KEGG）富集分析，用AutoDock软件通过分子对接验证五味子丙素与核心交集靶点的结合能力，并运用PyMol软件可视化分析。体外实验采用五味子丙素（25、50、100 μmol/L）处理人胶质瘤U251细胞，应用CCK-8、划痕实验、Western Blotting等方法检测五味子丙素对细胞增殖、迁移及蛋白表达的影响。结果 共筛选出药物靶点98个，疾病靶点3 230个，药物与疾病交集靶点63个，核心靶点为蛋白激酶B1（Akt1）、表皮生长因子受体（EGFR）、肉瘤病毒蛋白（SRC）、哺乳动物雷帕霉素靶蛋白（mTOR）、表皮生长因子受体2（ERBB2）、磷酸肌醇-3-激酶催化亚基α（PIK3CA）等。KEGG通路142条，主要包括磷脂酰肌醇-3激酶（PI3K）/Akt、Rap1和低氧诱导因子-1（HIF-1）信号通路等。体外研究发现，与对照组相比，五味子丙素50、100 μmol/L能抑制人胶质瘤U251细胞的增殖和迁移，且五味子丙素25、50、100 μmol/L均能显著降低PI3K/Akt通路相关蛋白p-Akt和p-ERK1/2蛋白的表达（P＜0.05、0.01、0.001）。结论 五味子丙素可能通过PI3K/Akt信号通路抑制人胶质瘤U251细胞的增殖和迁移。

Objective To investigate the anti-glioma effect of schisandrin C, and its mechanism based on network pharmacology, molecular docking technology and in vitro experimental validation. Methods Schisandrin C related targets were screened through databases such as TCMSP, and glioma related targets were collected using databases like GeneCards. The intersection targets between schisandrin C and glioma were identified and a Venn diagram was drawn. PPI network was constructed using the STRING database, and core intersection targets were screened using the Cytoscape software. GO and KEGG enrichment analyses of the intersecting targets were performed using the DAVID database. The binding ability of schisandrin C to the core intersection targets was verified by molecular docking using AutoDock software, and visualised and analysed using PyMol software. Finally, human glioma U251 cells were treated with schisandrin C (25, 50, and 100 μmol/L), and CCK-8, scratch assay and Western Blotting were applied to detect the effects of different concentrations of schisandrin C on cell proliferation, migration and protein expression. Results A total of 98 drug targets, 3 230 disease targets, and 63 drug-disease intersection targets were screened, and the core targets were Akt1, EGFR, SRC, mTOR, ERBB2, PIK3CA, etc. 142 KEGG pathways were identified, which mainly included PI3K/Akt, Rap1, and HIF-1 signalling pathways. In vitro studies found that compared with the control group, schisandrin C 50 and 100 μmol/L inhibited the proliferation and migration of human glioma U251 cells, and low, schisandrin C 25, 50, and 100 μmol/L groupsignificantly reduced the expression of PI3K/Akt pathway-related proteins (P < 0.05, 0.01, 0.001), p-Akt and p-ERK1/2 proteins. Conclusion Schisandrin C may inhibit the proliferation and migration of human glioma U251 cells through the PI3K/Akt signalling pathway.

R285.5

黑龙江省中医药管理局项目（ZHY2023-115）；齐齐哈尔市科技计划联合引导项目（LSFGG-2022049）；齐齐哈尔医学科学院临床科研基金项目（QMSI2019L-24）