基于网络药理学和分子对接技术探讨“半枝莲-山慈菇”抗乳腺癌的作用机制

目的通过网络药理学和分子对接方法探讨"半枝莲–山慈菇"抗乳腺癌的作用机制。方法通过中药系统药理学分析平台(TCMSP)筛选半枝莲、山慈菇的有效化学成分及相应靶蛋白。通过DrugBank、Uniprot数据库筛选乳腺癌潜在靶点,运用Cytoscape 3.8.0软件构建"化合物–靶点–疾病"网络图。使用STRING数据库绘制蛋白互作(PPI)网络,利用DAVID数据库对有效作用靶点进行GO功能、KEGG通路富集分析。结果共筛选出半枝莲中有效化学成分29个,山慈菇中有效化学成分3个;对应潜在作用靶点517个,乳腺癌靶点118个;将"半枝莲–山慈菇"与乳腺癌的靶点对比,获得8个药物–疾病共同靶点,包括雄激素受体(AR)、半胱氨酸天冬氨酸蛋白酶-3(CASP3)、半胱氨酸天冬氨酸蛋白酶-9(CASP9)、雌激素受体α(ESR1)、雌激素受体β(ESR2)、钾电压门控通道亚家族H成员2(KCNH2)、前列腺素G/H合酶2(PTGS2)和钠依赖性血清素转运体(SLC6A4)。GO功能分析得到197个条目,涉及药物代谢等方面。KEGG通路分析得到116个条目,涉及膀胱癌、非小细胞肺癌、胰腺癌、非洲锥虫病、前列腺癌、结直肠癌、子宫内膜癌等通路。结论研究揭示了"半枝莲–山慈菇"抗乳腺癌的关键靶点和涉及的生物学过程及信号通路,并结合分子对接技术,发现其作用是多靶点、多通路的,为今后的分子生物学实验奠定了基础。

Anti-breast cancer mechanism of Scutellaria barbata and Iphigenia indica based on network pharmacology and molecular docking technology

Objective To investigate the mechanism of "Scutellaria barbata and Iphigenia indica" against breast cancer by network pharmacology and molecular docking methods. Methods The effective chemical constituents and corresponding target proteins of Scutellaria barbata and Iphigenia indica were screened by TCMSP. The potential targets of breast cancer were screened by DrugBank and Uniprot databases, and the network diagram of "compound-target-disease" was constructed using Cytoscape 3.8.0 software. The protein interaction (PPI) network was mapped using the STRING database, and GO function and KEGG pathway enrichment analysis of effective targets were performed using the DAVID database. Results A total of 29 effective chemical components in Scutellaria barbata, 3 effective chemical components in Iphigenia indica, 517 potential targets corresponding to the above chemical components, and 118 breast cancer targets were selected. Eight drug-disease common targets were obtained by comparing "Scutellaria barbata and Iphigenia indica" with the targets of breast cancer, including AR, CASP3, CASP9, ESR1, ESR2, KCNH2, PTGS2, and SLC6A4. GO functional analysis resulted in 197 entries, involving aspects such as drug metabolism. KEGG pathway analysis yielded 116 items, involving bladder cancer, non-small cell lung cancer, pancreatic cancer, African trypanosomiasis, prostate cancer, colorectal cancer, endometrial cancer and other pathways. Conclusions Study preliminarily revealed the key targets and biological processes and signaling pathways involved in anti-breast cancer effect of "Scutellaria barbata and Iphigenia indica", and combined with molecular docking technology, found that its role is multi-target and multi-pathway, laying foundation for future molecular biology experiments.