柴胡皂苷D抑制PPA1诱导弥漫性大B细胞淋巴瘤细胞凋亡的研究  

Study on saikosaponin D-mediated inhibition of PPA1-induced apoptosis in diffuse large B-cell lymphoma

作　　者：潘静 孙园园 PAN Jing;SUN Yuan-yuan(Department of Hematology,First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China)

机构地区：[1]锦州医科大学附属第一医院血液内科,锦州121000

出　　处：《天然产物研究与开发》2025年第4期591-601,731,共12页Natural Product Research and Development

基　　金：辽宁省科技厅自然指导项目(2015020345);锦州医科大学横向课题(2022-002)。

摘　　要：本研究旨在探讨柴胡皂苷D(saikosaponin D,SD)通过调节无机焦磷酸酶1(inorganic pyrophosphatase,PPA1)对弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)细胞凋亡的影响。使用高表达PPA1的HBL-1和U2932细胞系,采用不同浓度的SD处理,通过MTT比色法和TUNEL染色法评估细胞的增殖与凋亡,并通过ELISA和WB分析PPA1的活性及相关蛋白表达。此外,本研究构建细胞移植瘤模型以进行体内验证。结果显示,SD可显著抑制细胞增殖,诱导凋亡,降低PPA1活性及表达,增加剪切的半胱天冬酶-3(cleaved cysteine-aspartic protease 3,cleaved Caspase-3)和B细胞淋巴瘤2相关X蛋白(Bcl-2-associated X protein,Bax)水平,减少B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)的表达。在细胞移植瘤模型中,PPA1下调组肿瘤体积显著低于PPA1下调对照组,SD处理组肿瘤体积亦显著低于DMSO溶剂对照组。综上所述,SD通过抑制PPA1促进DLBCL细胞凋亡,展现出作为抗DLBCL药物的潜力。This study aims to investigate the effects of saikosaponin D(SD)on the apoptosis of diffuse large B-cell lymphoma(DLBCL)through the inorganic pyrophosphatase 1(PPA1).This study utilized high PPA1-expressing cell lines,HBL-1 and U2932,treated with varying concentrations of SD.The proliferation and apoptosis of the cells were assessed using the MTT and TUNEL assay,while ELISA and WB were employed to analyze PPA1 activity and the expression of relevant proteins.Additionally,this study established a cell transplantation tumor model for in vivo validation.The results demonstrated that SD significantly inhibited cell proliferation and induced apoptosis by reducing activity and expression of PPA1,increasing levels of cleaved cysteine-aspartic protease 3(cleaved Caspase-3)and Bcl-2-associated X protein(Bax),and decreasing B-cell lymphoma 2(Bcl-2)expression.In the cell transplantation tumor model,the tumor volume in the PPA1 down-regulated group was significantly lower than that in the PPA1 down-regulated control group,and the tumor volume in the SD treatment group was also significantly reduced in comparison with DMSO control group.In summary,SD promotes apoptosis in DLBCL cells by inhibiting PPA1,highlighting its potential as an anti-DLBCL drug.

关 键 词：柴胡皂苷D 弥漫性大B细胞淋巴瘤 无机焦磷酸酶1 细胞凋亡 

分 类 号：R285[医药卫生—中药学]