Effect of Chlorambucil Combined with Ibrutinib on Mantle Cell Lymphoma Cell Line Jeko-1 and Its Related Mechanism
10.19746/j.cnki.issn1009-2137.2024.01.021
- VernacularTitle: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
- Author:
Ni-Na CAI
1
;
Wan-Yi LIU
;
Zhi-Qiang LIU
;
Jia-Hui GONG
;
Yi-Ling LIN
;
Ze-Chuan WANG
;
Yue-Qin HUANG
;
Jian-Xin GUO
Author Information
1. 福建医科大学附属第二医院血液科,福建泉州 362000
- Keywords:
mantle cell lymphoma;
chlorambucil;
ibrutinib;
cell apoptosis
- From:
Journal of Experimental Hematology
2024;32(1):132-137
- CountryChina
- Language:Chinese
-
Abstract:
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(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/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(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/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-l 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.
