目的 通过网络药理学分析结合实验验证探讨小白菊内酯在口腔癌中的作用机制。方法 利用SwissTargetPrediction、PharmMapper、GeneCards、OMIM、TTD等数据库筛选小白菊内酯与口腔癌的交集靶点，构建蛋白互作（PPI）网络并进行基因本体（GO）功能、京都基因和基因组百科全书（KEGG）富集分析，开展分子对接以评估小白菊内酯与核心靶点的结合能力，并通过Western bloting检测Cal-27细胞关键蛋白水平。结果 共获得57个药物–疾病共同靶点，其中表皮生长因子受体（EGFR）、Src酪氨酸蛋白激酶（SRC）、半胱天冬酶3（CASP3）在网络中处于关键节点位置，富集分析显示这些靶点显著参与细胞凋亡、蛋白质磷酸化、EGFR/ErbB家族信号、MAPK信号、焦点黏附及耐药相关通路。分子对接提示小白菊内酯能够与EGFR、SRC、CASP3等核心靶点稳定结合。体外实验进一步证实小白菊内酯下调EGFR、SRC蛋白相对表达水平，上调Caspase‑3蛋白表达水平，抑制细胞增殖与迁移并促进凋亡（P＜ 0.05、0.01）。结论 小白菊内酯通过多靶点协同作用，同时干预EGFR、SRC、CASP3等关键信号分子，阻断促增殖和促迁移通路并激活凋亡机制，从而发挥显著的抗口腔癌效应。

Objective To explore the mechanism of action of parthenolide in oral cancer through network pharmacological analysis combined with experimental verification. Methods The intersection targets of parthenolide and oral cancer were screened by using databases such as SwissTargetPrediction, PharmMapper, GeneCards, OMIM, and TTD. PPI network was constructed and GO function, KEGG enrichment analysis was conducted. Molecular docking was carried out to evaluate the binding ability of parthenolide to the core target, and the levels of key proteins in Cal-27 cells were detected by Western bloting. Results A total of 57 drug-disease common targets were obtained, among which EGFR, SRC, and CASP3 were at key node positions in the network. Enrichment analysis revealed that these targets were significantly involved in apoptosis, protein phosphorylation, EGFR/ErbB family signaling, MAPK signaling, focal adhesion and drug resistance-related pathways. Molecular docking suggests that parthenolide can stably bind to core targets such as EGFR, SRC, and CASP3. In vitro experiments further confirmed that parthenolide down-regulated the relative expression levels of EGFR and SRC proteins, up-regulated the expression level of Caspase-3 protein, inhibited cell proliferation and migration and promoted apoptosis (P <  0.05, 0.01). Conclusion Parthenolide exerts a significant anti-oral cancer effect by simultaneously intervening in key signaling molecules such as EGFR, SRC, and CASP3 through multi-target synergistic action, blocking proliferation-promoting and migration-promoting pathways and activating apoptotic mechanisms.

R287.7

安徽省高等学校自然科学研究项目（KJ2021ZD0088）