苯丁酸氮芥联合伊布替尼对套细胞淋巴瘤Jeko-1细胞株的作用及相关机制  

Effect of Chlorambucil Combined with Ibrutinib on Mantle Cell Lymphoma Cell Line Jeko-1 and Its Related Mechanism

作　　者：蔡妮娜 刘婉艺 刘志强 龚佳惠 林艺玲 王泽川 黄月琴[1] 郭健欣[1] CAI Ni-Na;LIU Wan-Yi;LIU Zhi-Qiang;GONG Jia-Hui;LIN Yi-Ling;WANG Ze-Chuan;HUANG Yue-Qin;GUO Jian-Xin(Department of Hematology,The Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属第二医院血液科,福建泉州362000

出　　处：《中国实验血液学杂志》2024年第1期132-137,共6页Journal of Experimental Hematology

基　　金：泉州市科技项目(2018N029S)。

摘　　要：目的:探讨苯丁酸氮芥联合伊布替尼对套细胞淋巴瘤Jeko-1细胞株的抑制作用及相关机制。方法:分别将不同浓度的苯丁酸氮芥、伊布替尼单药及两药联合作用于Jeko-1细胞株,采用CCK-8检测细胞增殖情况,同时采用Western blot检测细胞中BCL-2、caspase-3、PI3K、AKT、P-AKT蛋白表达的变化。结果:分别用苯丁酸氮芥(3.125、6.25、12.5、25、50μmol/L)及伊布替尼(3.125、6.25、12.5、25、50μmol/L)单药处理Jeko-1细胞株24、48和72 h后,细胞增殖均受到抑制,且抑制作用呈时间及剂量依赖性,两药联合时抑制作用更明显(均P<0.05)。与对照组相比,苯丁酸氮芥(3.125、6.25、12.5、25、50μmol/L)及伊布替尼(3.125、6.25、12.5、25、50μmol/L)单药组细胞凋亡率增加,呈剂量依赖性;与相应剂量(3.125、6.25、12.5μmol/L)单药组比较,两药联合应用组Jeko-1细胞株的凋亡率明显增加(均P<0.05)。与单药组相比,两药联合时可产生协同作用,Jeko-1细胞的caspase-3表达明显增强,BCL-2、PI3K、p-AKT/AKT表达明显减弱(均P<0.05)。结论:苯丁酸氮芥及伊布替尼能够促进套细胞淋巴瘤Jeko-1细胞株的凋亡,两药联合应用可以产生协同作用,其主要是通过AKT相关信号通路发挥作用。Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50μmol/L)and ibrutinib(3.125,6.25,12.5,25,50μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate<50%),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P<0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50μmol/L)and ibutinib(3.125,6.25,12.5,25,50μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P<0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-1 cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P<0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

关 键 词：套细胞淋巴瘤 苯丁酸氮芥 伊布替尼 细胞凋亡 

分 类 号：R733.1[医药卫生—肿瘤]