Research Centre, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People's Republic of China.
Drug Des Devel Ther. 2021 Mar 26;15:1333-1344. doi: 10.2147/DDDT.S302221. eCollection 2021.
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.
由于淋巴瘤发病率和死亡率高，因此被认为是全球最紧迫的健康问题之一。先前的研究表明，作为一种天然存在的化合物，杠柳毒苷可抑制几种癌症的生长并诱导其凋亡。然而，杠柳毒苷对淋巴瘤的作用及其潜在的作用机制尚不清楚。
使用 PharmMapper 数据库预测杠柳毒苷的潜在靶标。使用 GeneCard 数据库鉴定淋巴瘤相关基因。获得一些相交的基因，并使用 STRING 基因本体论分析可视化蛋白质-蛋白质相互作用网络。使用 R 项目进行京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路分析。使用 MTS 测定、流式细胞术、实时定量聚合酶链反应（qPCR）和 Western blot 来验证杠柳毒苷是否具有抗淋巴瘤活性。
共鉴定出 216 个相交基因。使用 Cytoscape 软件可视化了许多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排名的通路。使用 HuT 78 和 Jurkat 细胞系验证了预测结果。杠柳毒苷以剂量和时间依赖的方式显著抑制其增殖，但对外周血淋巴细胞的活力没有影响。流式细胞术显示，杠柳毒苷处理可增加 HuT 78 和 Jurkat 细胞的凋亡率和 G2/M 期的比例。CDK1 和周期蛋白 B1 复合物的形成是 G2/M 期有丝分裂分裂的关键守门员。Western blot 分析显示，杠柳毒苷显著降低了 CDK1 和周期蛋白 B1 的蛋白水平；然而，实时 qPCR 显示基因表达没有影响。
杠柳毒苷通过多个靶标和信号通路在淋巴瘤细胞中表现出抗肿瘤作用，可能成为治疗淋巴瘤的新型治疗剂。
