Effect of bromdomain protein 4 inhibitor GSK525762A on the proliferation and apoptosis of B-cell acute lymphoblastic leukemia cells and its mechanism.
- VernacularTitle:溴结构域蛋白4抑制剂GSK525762A对急性B淋巴细胞白血病细胞增殖和凋亡的影响及可能机制
- Author:
Man WANG
1
;
Chong CHEN
1
;
Jie XU
1
;
Li WANG
1
;
Xuguang SONG
1
;
Huanxin ZHANG
1
;
Lingyu ZENG
1
;
Kailin XU
1
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; drug effects; Benzodiazepines; pharmacology; Caspase 3; metabolism; Cell Line, Tumor; Cell Proliferation; drug effects; Humans; Leukemia, B-Cell; metabolism; pathology; Proto-Oncogene Proteins c-bcl-2; metabolism
- From: Chinese Journal of Hematology 2014;35(6):528-532
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of bromdomain protein 4 (BRD4) inhibitor GSK525762A on the proliferation, apoptosis of B-cell acute lymphoblastic leukemia cell line RS4;11 cells, and to further explore the mechanism.
METHODSCompared with Jurkat leukemia cells, the activity of BRD4 on RS4; 11 cells were inhibited by the inhibitor GSK525762A. The inhibitory effects of BRD4 on RS4; 11 cells were measured by CCK-8 test and the apoptosis of those cells was determined by AnnexinV/7-AAD dyeing using flow cytometry. The transcripts of anti-apoptotic genes c-myc, Bcl-2, CDK6 and proapoptotic genes Bad, Bak, Bax were detected by quantitative PCR, and the expression of Bcl-2 and Bak proteins were detected via Western blot.
RESULTSProliferation of RS4;11 cells could be inhibited by GSK525762A in a time- and dose-dependent manner, and the inhibitory IC50 at 48 and 72 h was 6.174 and 1.996 μmol/L, respectively. Compared with DMSO in control group, the levels of c-myc, Bcl-2 and CDK6 mRNA transcripts in RS4; 11 cells were reduced in GSK525762A treated group, while the levels of Bad, Bak, Bax mRNA transcripts were enhanced,moreover, Bcl- 2 protein levels decreased and Bak protein levels increased. However, the inhibitory effect of GSK525762A on Jurkat cells proliferation was not obvious.
CONCLUSIONGSK525762A can inhibit the proliferation of RS4; 11 cells and promoted cells apoptosis. The possible mechanisms underlying this phenomenon might be achieved via downregulation of Bcl-2 protein induced apoptosis of leukemia cells.