目的 通过网络药理学、分子对接技术探讨澳洲茄边碱治疗三阴性乳腺癌的潜在靶点和作用机制。方法 通过PharmMapper、Stitch、TCMSP、Herb、SEA数据库收集澳洲茄边碱的药物靶点，在GeneCards、OMIM、TTD数据库筛选三阴性乳腺癌相关疾病靶点，利用Venny 2.1.0平台提取二者交集靶点，运用STRING平台构建交集靶点的蛋白相互作用（PPI）网络，预测核心靶点，通过Metascape数据库对交集靶点进行基因本体（GO）功能富集分析及京都基因与基因组百科全书（KEGG）通路富集分析，经微生信在线工具绘制条形图和气泡图。由Auto Dock Vina和PyMOL进行分子对接。结合GEO、GEPIA2等数据库进行单基因差异表达和生存分析。结果 澳洲茄边碱337个潜在靶点，三阴性乳腺癌相关靶点4 882个，交集靶点162个，核心靶点包括表皮生长因子受体（EGFR）、热休克蛋白90α家族A类成员1（HSP90AA1）、蛋白激酶B1（Akt1）、肉瘤病毒癌基因同源物（SRC）等46个核心靶点。GO和KEGG分析显示，澳洲茄边碱可能通过癌症通路、PI3K/Akt、MAPK等信号通路治疗三阴性乳腺癌。分子对接结果显示澳洲茄边碱与前4个核心靶点结合能均小于−10 kcal/mol。结论 澳洲茄边碱可通过多靶点、多通路发挥治疗三阴性乳腺癌作用。

Objective To explore the potential targets and mechanisms action of solamargine in treatment of triple-negative breast cancer through network pharmacology and molecular docking techniques. Methods The drug targets of solamargine were collected through the PharmMapper, Stitch, TCMSP, Herb, and SEA databases. The disease targets related to triple-negative breast cancer were screened in the GeneCards, OMIM and TTD databases. The intersection targets of the two were extracted using the Venny 2.1.0 platform. The STRING platform was used to construct the PPI network of the intersection targets, predict the core targets, and conduct GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersection targets through the Metascape database. Bar charts and bubble charts were drawn using the wechat online tool. Molecular docking was performed by Auto Dock Vina and PyMOL. Single-gene differential expression and survival analysis were conducted in combination with databases such as GEO and GEPIA2. Results A total of 337 potential targets of solamargine and 4 882 triple-negative breast cancer -related targets were identified, with 162 overlapping targets. The core targets included 46 key molecules such as EGFR, HSP90AA1, Akt1, SRC. GO and KEGG enrichment analyses revealed that solanidine may exert therapeutic effects on triple-negative breast cancer through signaling pathways including cancer-related pathways, PI3K/Akt, and MAPK. Molecular docking results showed that the binding energies of solanidine with the top 4 core targets were all less than −10 kcal/mol. Conclusion Solamargine may exert therapeutic effects on triple-negative breast cancer through a multi-target and multi-pathway mechanism.

R287.4

江西省中医药管理局科技计划课题（2021B605）