中药新药与临床药理2025，Vol.36Issue(6)：843-851,9.DOI:10.19378/j.issn.1003-9783.2025.06.001
重楼皂苷Ⅱ促进弥漫大B淋巴瘤细胞凋亡的作用及机制
The Role and Mechanism of PolyphyllinⅡ in Promoting Apoptosis in Diffuse Large B-Cell Lymphoma Cells
摘要
Abstract
Objective To investigate the role and mechanism of PolyphyllinⅡ(PPⅡ)in promoting apoptosis in diffuse large B-cell lymphoma(DLBCL)cells.Methods Human DLBCL cell lines U2932 and TMD-8 were treated with 0,0.25,0.5,1,2,and 4 µmol·L-1 PPⅡ for 24 hours.Cell viability was detected using the CCK-8 assay;apoptosis was measured by Annexin V-FITC/PI flow cytometry;and nuclear apoptosis and cell count were observed using Hoechst 33342 staining.Differentially expressed genes(DEGs)in DLBCL were screened and enriched using The Cancer Genome Atlas(TCGA)database.The Swiss Target Prediction database was used to predict the targets of PPⅡ.The intersection of predicted PPⅡ targets and DLBCL DEGs was identified,and a protein-protein interaction(PPI)network was constructed to screen key targets,followed by molecular docking validation.Western Blot was used to verify the effects of PPⅡ on the expression of key target proteins.Results Compared with the control group(0 µmol·L-1),the viability of U2932 and TMD-8 cells in the 0.25,0.5,1,2,and 4 µmol·L-1 PPⅡ groups was significantly reduced(P＜0.05,P＜0.01).The apoptosis rate of U2932 and TMD-8 cells in the 1 and 2 µmol·L-1 PPⅡgroups was significantly increased(P＜0.01).As the concentration of PPⅡ increased,nuclear apoptosis in U2932 and TMD-8 cells became more evident,with fragmented nuclear staining observed.The number of U2932 and TMD-8 cells in the 0.5,1,and 2 µmol·L-1 PPⅡ groups was significantly reduced(P＜0.01).A total of 6 250 DEGs were identified,and enrichment analysis revealed a close relationship between DLBCL and apoptosis signaling pathways.Five key targets,including Caspase-9,Caspase-3,Caspase-7,Bax,and Bcl-2,were screened.Molecular docking showed that PPⅡ had good binding activity with the key targets Caspase-9,Caspase-3,and Caspase-7.Western Blot results showed that,compared with the control group,the protein expressions of Cleaved Caspase-9/Caspase-9,Cleaved Caspase-3/Caspase-3,Cleaved Caspase-7/Caspase-7,and Bax/Bcl-2 in U2932 and TMD-8 cells in the 0.5,1,and 2 µmol·L-1 PPⅡ groups were significantly upregulated(P＜0.05,P＜0.01).Conclusion PPⅡ can inhibit the proliferation of DLBCL cells and promote their apoptosis by inducing the Caspase cascade reaction.关键词
重楼皂苷Ⅱ/弥漫大B细胞淋巴瘤/U2932 细胞/TMD-8 细胞/Caspase级联反应/细胞增殖/细胞凋亡Key words
PolyphyllinⅡ/diffuse large B-cell lymphoma/U2932 cells/TMD-8 cells/Caspase cascade reaction/cell proliferation/cell apoptosis分类
医药卫生引用本文复制引用
刘玉莲,彭纪铭,王志强,刘代利,伏瑶..重楼皂苷Ⅱ促进弥漫大B淋巴瘤细胞凋亡的作用及机制[J].中药新药与临床药理,2025,36(6):843-851,9.基金项目
山东省自然科学基金青年基金项目(ZR2022QH168) （ZR2022QH168）
江苏省新药研究与临床药学重点实验室开放课题(XZSYSKF2021033). （XZSYSKF2021033）
