卷柏总双黄酮有效部位通过抑制PI3K/AKT通路抗弥漫大B细胞淋巴瘤  

The effective parts of total biflavones from selaginella inhibit diffuse large B-cell lymphoma by down-regulating PI3K/AKT pathway

作　　者：苏畅 徐康平 卢桂阁 胡倩宇 朱雪婷 王彩琴 贺怡子 曾若兰 李亚军 肖玲[2] 周辉 SU Chang;XU Kangping;LU Guige;HU Qianyu;ZHU Xueting;WANG Caiqin;HE Yizi;ZENG Ruolan;LI Yajun;XIAO Ling;ZHOU Hui(Department of Lymphoma and Hematology,the Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University/Hunan Cancer Hospital,Changsha,410031,Hunan,China;Department of Histology and Embryology,Xiangya School of Medicine,Central South University,Changsha,410013,Hunan,China;Xiangya School of Pharmacy,Central South University,Changsha,410013,Hunan,China;Graduate Collaborative Training Base of Hunan Cancer Hospital,Hengyang Medical School,University of South China,Hengyang,421099,Hunan,China)

机构地区：[1]中南大学湘雅医学院附属肿瘤医院/湖南省肿瘤医院,淋巴瘤血液内科,湖南长沙410013 [2]中南大学湘雅医学院,组织学与胚胎学系,湖南长沙410013 [3]中南大学湘雅药学院,湖南长沙410013 [4]南华大学衡阳医学院,湖南省肿瘤医院研究生协作培养基地,湖南衡阳421099

出　　处：《肿瘤药学》2024年第4期442-447,共6页Anti-Tumor Pharmacy

基　　金：湖南省中医药管理局一般项目(D2022074);湖南省卫生健康委一般项目(202203045455);湖南省自然科学基金(2022JJ30026);湖南省自然科学基金(2022JJ30789);中南大学中央高校基础研究基金(2023ZZTS0867);中南大学中央高校基础研究基金(2024ZZTS0918);湖南省卫健委技术厅资助项目(WZ2020-13);长沙血液病精准诊疗技术创新中心([2024]NO.196)。

摘　　要：目的探究卷柏总双黄酮(TBF)有效部位治疗弥漫大B细胞淋巴瘤(DLBCL)的作用及可能机制。方法采用CCK-8法检测TBF有效部位对DLBCL细胞增殖的影响;流式细胞术检测TBF有效部位对DLBCL细胞凋亡及周期的影响;转录组学测序并富集差异基因,初步探讨TBF有效部位抗DLBCL的作用机制;Western blotting验证TBF有效部位影响的信号通路。结果TBF有效部位对DLBCL不同亚型细胞株的增殖均有显著抑制作用,且可诱导DLBCL细胞凋亡,将细胞周期阻滞于G_(2)期。TBF有效部位主要对细胞内PI3K/AKT信号通路产生影响。随着TBF有效部位浓度的增加,PI3K、AKT的表达量及p-PI3K、p-AKT与对照组相比显著降低。结论TBF有效部位可通过抑制PI3K/AKT信号通路激活发挥抗DLBCL作用,为DLBCL临床治疗提供了新策略。Objective To explore the effects and mechanism of total biflavonoids(TBF)effective parts extracted from Se-laginella tamariscina on diffuse large B-cell lymphoma(DLBCL).Methods CCK-8 method was used to detect the effects of TBF effective parts on the proliferation of DLBCL cells.Flow cytometry was applied to detect the apoptosis and cell cycle of cells after treated by TBF effective parts.Transcriptome sequencing and enrichment of differential genes were conducted to preliminarily explore the mechanism of TBF effective parts in anti-DLBCL.Western blotting was used to verify the signaling pathways affected by TBF effective parts.Results The TBF effective parts significantly inhibited the proliferation of different types of DLBCL cell lines,induced an increase in the proportion of apoptosis of DLBCL cells,and blocked the cell cycle in G_(2) phase.The TBF effective parts mainly affected the intracellular PI3K-AKT signaling pathway.Compared with the control group,the expression of PI3K and AKT,as well as their phosphorylated forms(p-PI3K and p-AKT),were significantly decreased in a TBF effective parts concentration-dependent manner.Conclusion The TBF effective parts played an anti-DLBCL role by inhib-iting the activation of the PI3K/AKT signaling pathway.TBF effective parts may serve as a new option for the treatment of DLBCL.

关 键 词：卷柏 总双黄酮 弥漫大B细胞淋巴瘤 凋亡 PI3K/AKT信号通路 

分 类 号：R733.4[医药卫生—肿瘤]