Ibrutinib inhibits diffuse large B-cell lymphoma cell survival
10.3969/j.issn.1000-8179.2017.18.676
- VernacularTitle:Ibrutinib抑制弥漫大B细胞淋巴瘤细胞生存的作用研究
- Author:
WU DONGWEI
1
;
XIA BING
;
WU LING
;
XU WEN
;
NING QIAOYANG
;
YUAN TIAN
;
WANG CHAOYU
;
JIN XIN
;
YU YONG
;
ZHANG YIZHUO
Author Information
1. 天津医科大学肿瘤医院血液科
- Keywords:
diffuse large B-cell lymphoma;
ibrutinib;
proliferation;
apoptosis
- From:
Chinese Journal of Clinical Oncology
2017;44(18):903-908
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To illustrate the effect and mechanism of ibrutinib,a Bruton's tyrosine kinase(BTK)inhibitor that inhibits diffuse large B-cell lymphoma(DLBCL)cell survival.Methods:DLBCL cell lines SUDHL-10 and HBL-1 were treated with ibrutinib at different concentrations.A MTT assay was used to detect the inhibition of cell proliferation.Cell apoptosis was analyzed by Annexin V-binding assay,as well as flow cytometry and DAPI staining.The expression of phosphorylated BTK,AKT and ERK was detected by Western blot. DLBCL cells were co-cultured with MSC.The inhibitory effect of ibrutinib on DLBCL cells in tumor microenvironment was assessed in clonogenicity in vitro and in a tumor-bearing non-obese diabetic/severe combined immunodeficient mice in vivo.Results:Up to 2.5 μmol/L and high concentrations of ibrutinib significantly inhibited the proliferation of DLBCL cells in a dose-dependent manner.Approx-imately 1 and 2.5 μmol/L ibrutinib was added on SUDHL-10 cells for 24 h,and the cell apoptotic rates were(21.73±3.64)% and(34.71± 2.36)%,respectively.Both were superior to that of the control group(3.55±1.89)%(P<0.05).Both two DLBCL cell lines pretreated with 5 and 10 μmol/L ibrutinib for 24 h and exhibited nuclear shrinkage at 5 μmol/L and nuclear fragmentation at 10 μmol/L.The expres-sion of phosphorylated BTK,AKT,and ERK decreased significantly after ibrutinib treatment.Ibrutinib inhibited clonogenicity in vitro(P<0.01)and cell proliferation and growth in vivo of DLBCL cells in co-culture system.The differences were statistically significant.Conclu-sion:Ibrutinib can inhibit the proliferation and induce apoptosis of SUDHL-10 and HBL-1 cell lines through a mechanism of blocking the AKT and ERK signaling pathways,as well as the proliferation of DLBCL cells in tumor microenvironment.This finding can significant-ly benefit DLBCL treatment.
