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.