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西黄丸抗弥漫大B细胞淋巴瘤的作用机制预测与验证
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| 篇名： | 西黄丸抗弥漫大B细胞淋巴瘤的作用机制预测与验证 |
| TITLE： | Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma |
| 摘要： | 目的 探讨西黄丸抗弥漫大B细胞淋巴瘤（DLBCL）的作用机制。方法基于TCMSP、GeneCards、DisGeNET等数据库筛选西黄丸活性成分及DLBCL相关疾病靶点；利用String数据库和Cytoscape软件，构建蛋白质-蛋白质相互作用网络以筛选核心成分与核心靶点，然后进行基因本体功能和京都基因与基因组数据库通路富集分析；利用GEPIA和PanCanSurvPlot数据库分析核心靶点的临床相关性；进一步对核心成分与核心靶点进行分子对接和分子动力学模拟验证，并采用分子力学泊松-玻尔兹曼表面积（MM-PBSA）算法计算结合自由能。采用CCK-8法、流式细胞术及Westernblot法验证西黄丸对DLBCL的作用及相关分子机制。结果网络药理学共筛选出108个西黄丸活性成分和410个西黄丸治疗DLBCL的潜在靶点，获得17beta-estradiol（17β-雌二醇）、quercetin（槲皮素）等6个核心成分，肿瘤蛋白53（TP53）、酪氨酸蛋白激酶Src（SRC）等10个核心靶点。富集分析显示，西黄丸抗DLBCL主要涉及凋亡信号通路、磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路等。临床相关性分析显示，TP53、SRC在DLBCL样本中高表达，且与患者不良预后相关（P＜0.05）。分子对接、分子动力学模拟及MM-PBSA结合自由能计算证实，SRC-槲皮素复合物具有更强而稳定的结合亲和力。体外实验结果显示，西黄丸可浓度依赖性抑制DLBCL细胞的增殖；与对照组比较，西黄丸中、高浓度组可显著诱导SU-DHL2和SU-DHL4细胞凋亡，显著降低SU-DHL4细胞中SRC蛋白、磷酸化PI3K（p-PI3K）/PI3K、p-Akt/Akt的表达（P＜0.05）。结论西黄丸可能通过调控SRC/PI3K/Akt信号通路抑制DLBCL细胞增殖并诱导其凋亡。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway. |
| 期刊： | 2026年第37卷第02期 |
| 作者： | 黄茹意；李金宇；林文琪；江鑫；陈燕玲；黄伟昆；杨琳 |
| AUTHORS： | HUANG Ruyi，LI Jinyu，LIN Wenqi，JIANG Xin，CHEN Yanling，HUANG Weikun，YANG Lin |
| 关键字： | 西黄丸；弥漫大B细胞淋巴瘤；网络药理学；分子对接；分子动力学模拟 |
| KEYWORDS： | Xihuang pill； diffuse large B-cell lymphoma； network pharmacology； molecular docking； molecular dynamics |
| 阅读数： | 3 次 |
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