title: [Effect of BRD4 inhibitor GSK525762A on proliferation and apoptosis of KU812 leukemic cells and its mechanism].
abstract: This study was purposed to investigate the effect of bromodomain-containing protein 4 (BRD4) inhibitor GSK525762A on the proliferation and apoptosis of chronic myeloid leukemia blast crisis KU812 cells and its mechanism. KU812 cells were treated with different concentrations of GSK525762A (100, 250, 500, 1 000, 2 500 and 5000 nmol/L) and the inhibitory effects of drug on KU812 cell proliferation after 48 and 72 hours were detected by using CCK-8 assay. KU812 cells were treated with 3 different concentrations of GSK525762A (1.0, 2.5 and 5 µmol/L) and the cell apoptosis after 72 hours were assayed by using flow cytometry. KU812 cells were treated with DMSO and 2.5 µmol/L GSK525762A, and the mRNA levels of C-MYC, BCL-2, CDK6, BCL-xL, BAK and BAX were determined by using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results showed that GSK525762A could significantly inhibit the proliferation of KU812 cells and the inhibitory effect on KU812 cell proliferation was dependent on the dose-course and time-course of GSK525762A treatment. GSK525762A treatment could induce apoptosis of KU812 cells in a dose-dependent manner. After GSK525762A treatment, the mRNA levels of proliferation-promoting genes ( C-MYC and CDK6) and pro-survival genes ( BCL-2 and BCL-xL) decreased, while the transcription level of pro-apoptosis genes BAK and BAX increased, as compared to that of the control group. It is concluded that GSK525762A can inhibit the proliferation of KU812 cells and induce cell apoptosis possibly through depressing the transcription of C-MYC, BCL-2, CDK6 and BCL-xL gene, and down-regulating BAK and BAX transcription.
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China; Department of Oncology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Song
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Zeng
authors.affiliation: Department of Oncology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China. E-mail: cnhzxyq@163.com.
authors.forename: Zheng-Xiang
authors.initials: ZX
authors.lastname: Han
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Hematology, Xuzhou Medical College Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D000092468:Bromodomain Containing Proteins
chemical_list: D001569:Benzodiazepines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C554645:molibresib