title: [Effect of bromdomain protein 4 inhibitor GSK525762A on the proliferation and apoptosis of B-cell acute lymphoblastic leukemia cells and its mechanism].
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Compared 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.
  
  
  RESULTS
  Proliferation 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.
  
  
  CONCLUSIONS
  GSK525762A 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.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Huanxin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D001569:Benzodiazepines; C554645:molibresib; C505407:CASP3 protein, human; D053148:Caspase 3