目的 采用网络药理学结合细胞学实验方法，初步探讨石蒜碱抗脑膜瘤的作用及潜在分子机制。方法 通过PubChem获取石蒜碱结构信息，联合Pharmmapper、SwissTargetPrediction、Similarity Ensemble Approach（SEA）及CTD数据库预测药物潜在靶点；并整合GeneCards、OMIM与CTD数据库获取脑膜瘤相关靶点，采用Venny构建交集靶点，利用STRING/Cytoscape进行蛋白质-蛋白质相互作用（PPI）网络拓扑分析，基于度（Degree）值、介数中心性（BC）和紧密中心性（CC）联合筛选核心靶点，进一步开展基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析和分子对接验证。随后采用体外实验评估石蒜碱对脑膜瘤CH157细胞增殖、克隆形成、侵袭、周期和凋亡的影响，并通过Western blotting检测Wnt/β-Catenin及磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（Akt）通路相关蛋白表达；最后通过LiCl回补实验验证Wnt/β-catenin通路的作用。结果 网络药理学结果显示，石蒜碱与脑膜瘤共有36个交集靶点，核心潜在靶点包括AKT1、转化生长因子-β1（TGFB1）、信号转导及转录激活蛋白3（STAT3）、基质金属蛋白酶9（MMP9）、非受体酪氨酸蛋白激酶（SRC）和糖原合成激酶3β（GSK3B），富集通路涉及PI3K-Akt、丝裂原活化蛋白激酶（MAPK）、癌症相关通路及细胞凋亡/迁移相关生物过程。体外实验显示，石蒜碱可显著抑制CH157细胞增殖、集落形成、迁移及侵袭，诱导细胞凋亡并影响细胞周期；Western blotting结果提示石蒜碱可抑制Wnt/β-Catenin及PI3K/Akt信号活化。结论 石蒜碱可能通过多靶点、多通路协同作用发挥抗脑膜瘤活性，其中Wnt/β-Catenin与PI3K/Akt信号通路可能是其重要作用环节。

Objective To preliminarily explore the anti-meningioma effect and potential molecular mechanism of lycorine by integrating network pharmacology with cytological experiments. Methods The potential targets of lycorine were predicted using Pharmmapper, SwissTargetPrediction, SEA and CTD databases, while meningioma-related targets were collected from GeneCards, OMIM and CTD. Intersecting targets were analyzed by Venny, STRING and Cytoscape, followed by GO/KEGG enrichment analysis and molecular docking. In vitro assays were performed to evaluate the effects of lycorine on proliferation, colony formation, invasion, cell cycle progression and apoptosis of CH157 cells. Western blotting was further used to detect Wnt/β-catenin- and PI3K/Akt-related proteins, and LiCl rescue experiments were performed to validate the role of Wnt/β-catenin signaling. Results A total of 36 intersecting targets were obtained, and AKT1, TGFB1, STAT3, MMP9, SRC and GSK3B were identified as core targets. These targets were enriched in PI3K-Akt, MAPK and cancer-related pathways. Experimental results showed that lycorine significantly inhibited malignant phenotypes of CH157 cells and promoted apoptosis. Western blotting indicated that lycorine suppressed activation of Wnt/β- catenin and PI3K/Akt signaling. Conclusion Lycorine may exert anti-meningioma activity through multi-target and multi-pathway regulation, with Wnt/β-catenin and PI3K/Akt pathways serving as important mechanistic links.

R285.5

武汉市卫生健康委员会面上项目（WZ24A09）；国家自然科学基金委青年项目（32000282）