Inhibitory Effects of Periplocin on Lymphoma Cells: A Network Pharmacology Approach and Experimental Validation.
Inhibitory Effects of Periplocin on Lymphoma Cells: A Network Pharmacology Approach and Experimental Validation.
复制标题
DOI：
10.2147/dddt.s302221
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Shan B
中科院分区：
文献类型：
--
作者：
Zhao R;Han C;Dai S;Wei S;Xiang X;Wang Y;Zhao R;Zhao L;Shan B
淋巴瘤因其高发病率和死亡率被认为是世界范围内最紧迫的健康问题之一。先前的研究表明，一种天然化合物periplocin可以抑制几种癌症的生长并诱导细胞凋亡。然而，periplocin对淋巴瘤的作用及其潜在的作用机制尚不清楚。使用PharmMapper数据库预测periplocin的潜在靶点。GeneCard数据库用于鉴定淋巴瘤相关基因。通过STRING基因本体分析，获得了部分交叉基因，并对蛋白-蛋白相互作用网络进行了可视化分析。京都基因和基因组百科全书路径分析使用R项目。采用MTS法、流式细胞术、实时定量聚合酶链反应（qPCR）、Western blotting等方法验证哌替星是否具有抗淋巴瘤活性。共鉴定出216个交叉基因。使用Cytoscape软件可视化了许多与癌症相关的信号通路，其中PI3K-Akt信号通路是与细胞增殖、凋亡和细胞周期进展相关的最高级通路。HuT 78和Jurkat细胞系被用来验证这些预测。Periplocin对外周血淋巴细胞增殖有明显的抑制作用，且呈剂量和时间依赖性，但对外周血淋巴细胞活力无影响。流式细胞术显示，培替星可提高G2/M期HuT 78和Jurkat细胞的凋亡率和凋亡比例。CDK1和细胞周期蛋白B1复合物的形成是G2/M期有丝分裂的关键看门人。Western blot分析显示，periplocin显著降低CDK1和cyclin B1蛋白水平；而real-time qPCR结果显示，对基因表达无影响。Periplocin通过多种靶点和信号通路对淋巴瘤细胞表现出抗肿瘤作用，有望成为治疗淋巴瘤的新型药物。
Lymphoma is considered to be one of the most pressing health problems worldwide owing to its high incidence and mortality. Previous studies have shown that periplocin, a naturally occurring compound, inhibits growth and induces apoptosis in several cancers. However, the effects of periplocin on lymphoma and the underlying mechanisms of action remain unclear. The PharmMapper database was used to predict the potential targets of periplocin. The GeneCard database was used to identify lymphoma-related genes. A few intersecting genes were obtained, and the protein-protein interaction network was visualized using STRING Gene ontology analysis. Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using R project. MTS assay, flow cytometry, real-time quantitative polymerase chain reaction (qPCR), and Western blotting were used to verify whether periplocin possesses anti-lymphoma activity. A total of 216 intersecting genes were identified. Numerous cancer-related signaling pathways were visualized using Cytoscape software, with the PI3K-Akt signaling pathway being the highest-ranked pathway related to cell proliferation, apoptosis, and cell cycle progression. HuT 78 and Jurkat cell lines were used to verify the predictions. Periplocin significantly inhibited their proliferation in a dose- and time-dependent manner, but had no effect on the viability of peripheral blood lymphocytes. Flow cytometry revealed that treatment with periplocin increased the apoptotic rate and ratio of HuT 78 and Jurkat cells in the G2/M phase. CDK1 and cyclin B1 complex formation is a key gatekeeper to mitotic division in the G2/M phase. Western blot analysis revealed that periplocin significantly decreased the protein levels of CDK1 and cyclin B1; however, real-time qPCR revealed no effect on gene expression. Periplocin showed anti-tumor effects in lymphoma cells through multiple targets and signaling pathways, and could be a novel therapeutic agent for the treatment of lymphoma.