WANG Jianv, LIU Li, XIONG Xia, et al. Novel small molecule inhibitor 15h induces cell apoptosis in diffuse large B-cell lymphoma cells by targeting BRD4. [J]. Journal of Southwest Medical University 46(5):413-417(2023)
DOI:
WANG Jianv, LIU Li, XIONG Xia, et al. Novel small molecule inhibitor 15h induces cell apoptosis in diffuse large B-cell lymphoma cells by targeting BRD4. [J]. Journal of Southwest Medical University 46(5):413-417(2023) DOI: 10.3969/j.issn.2096-3351.2023.05.009.
Novel small molecule inhibitor 15h induces cell apoptosis in diffuse large B-cell lymphoma cells by targeting BRD4
Objective The objective of this study was to investigate the impact of a novel small molecule inhibitor,15h,target⁃ ing bromodomain-containing protein 4 (BRD4),on apoptosis in diffuse large B-cell lymphoma (DLBCL) cells and explore its prelimi⁃ nary mechanism of action. Methods Firstly,the Alphascreen assay was used to explore the targeted inhibitory effect of 15h on BET family members,and the effect of 15h on cell viability in various hematologic malignancy cell lines was assessed using the MTT method. Flow cytometry was employed to examine the effect of 15h on DLBCL cell apoptosis. Finally,Western blot and qRT-PCR analyses were conducted to evaluate the regulatory effects of 15h on apoptosis-related proteins,including Bcl-2,Bax,and transcrip⁃ tion factor C-Myc. Results 15h primarily targeted and inhibited the BET protein family member BRD4,exhibiting a time- and concentration-dependent inhibitory effect on OCI-LY10 cell viability. Compared to the control group,the apoptotic rate gradually in⁃ creased from (4.612 ± 0.13)% to (50.7 ± 4.35)% (P < 0.05). Western blot and qRT-PCR analyses demonstrated that 15h treatment sup⁃ pressed the expression of the transcription factor C-Myc while up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2 in OCI-LY10 cells. Conclusion The novel small-molecule inhibitor,15h,might exert its effects by tar⁃ geting the binding of BRD4 to the transcription factor C-Myc,thereby inhibiting C-Myc gene transcription and ultimately inducing apoptosis in DLBCL cells.
关键词
弥漫性大B 细胞淋巴瘤BRD4c-Myc细胞凋亡
Keywords
Diffuse large B-cell lymphoma (DLBCL)BRD4c-MycCell apoptosis