基于系统药理学研究水飞蓟治疗肺癌的作用机制

目的 研究水飞蓟Silybum marianum对肺癌的作用及其机制。方法 利用中药系统药理学数据库（traditional Chinese medicine systems pharmacology,TCMSP）筛选水飞蓟的活性成分，并利用加权整体相似度法（weighted ensemble similarity,WES）和系统药物靶向工具（systematic drug targeting,SysDT）模型预测候选活性成分的靶点；进行基因本体论生物学过程（gene ontology biological process,GO BP）与京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析揭示靶点所涉及BP以及通路。选取水飞蓟主要活性成分水飞蓟宾进行体内外实验验证，首先验证水飞蓟宾对人肺腺癌H1975细胞与小鼠肺癌LLC细胞的体外抑制率；其次用流式细胞术评估水飞蓟宾对肿瘤细胞系的促凋亡作用；随后在LLC肺癌动物模型进行体内抑瘤验证，并检测瘤内细胞毒性T淋巴细胞（cytotoxic T cell,CD8+T）的浸...

Mechanisms of Silybum marianum on lung cancer based on system-pharmacology dissection

Objective To study the effect and mechanism of Silybum marianumon lung cancer. Methods Candidate active ingredients of S. marianum were screened out by traditional Chinese medicine systems pharmacology (TCMSP), targets were baited through weighted ensemble similarity (WES) and systematic drug targeting (SysDT) models; Gene ontology biological process (GOBP) and Kyoto encyclopedia of genes and genomes (KEGG) pathways of obtained targets were then top enriched. Silybin, the main active compound of S. marianum, was selected to test in vivo and in vitro experiments. Firstly, inhibitory rate of silybin on human lung adenocarcinoma cell (H1975) and mouse lung cancer cell (LLC) in vitro was verified; Secondly, apoptosis of silybin was evaluated by flow cytometry; Tumor inhibition in vivo was validated in non-small cell lung cancer mouse model, infiltration of cytotoxic T cell (CD8⁺ T) cells in tumor was detected; Finally, expressions of apoptosis-related proteins in tumor cells and tissues were verified by Western blotting. Results Twelve candidate active compounds and 355 targets were obtained, and compound-target network was constructed. The results of CCK-8 showed that silybin inhibited lung cancer cells in a dose-dependent manner, the data of flow cytometryin vitro and in vivo showed that silybin could promote the apoptosis of cancer cells by promoting the infiltration of CD8⁺ T cells in tumor cells; Silybin up-regulated p53 protein expression level in tumor cells and tumor tissues (P < 0.001), and down-regulated B-cell lymphoma 2 (Bcl-2) protein expression level (P < 0.05, 0.001). Conclusion S. marianum mainly exerts anti-tumor effects through regulating apoptosis-related pathways.