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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.8 P.666-681


HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression

Author(s):  Cancan LUO, Tiantian YU, Ken H. YOUNG, Li YU

Affiliation(s):  Department of Hematology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China; more

Corresponding email(s):   ndefy02021@ncu.edu.cn

Key Words:  Diffuse large B-cell lymphoma (DLBCL), Histone deacetylase (HDAC) inhibitor, Venetoclax, MYC, BCL2, TP53

Cancan LUO, Tiantian YU, Ken H. YOUNG, Li YU. HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression[J]. Journal of Zhejiang University Science B, 2022, 23(8): 666-681.

@article{title="HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression",
author="Cancan LUO, Tiantian YU, Ken H. YOUNG, Li YU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression
%A Cancan LUO
%A Tiantian YU
%A Li YU
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 8
%P 666-681
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200016

T1 - HDAC inhibitor chidamide synergizes with venetoclax to inhibit the growth of diffuse large B-cell lymphoma via down-regulation of MYC, BCL2, and TP53 expression
A1 - Cancan LUO
A1 - Tiantian YU
A1 - Ken H. YOUNG
A1 - Li YU
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 8
SP - 666
EP - 681
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200016

diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin’s lymphoma. A total of 10%‒15% of DLBCL cases are associated with myelocytomatosis viral oncogene homolog (MYC) and/or B-cell lymphoma-2 (BCL2) translocation or amplification. BCL2 inhibitors have potent anti-tumor effects in DLBCL; however, resistance can be acquired through up-regulation of alternative anti-apoptotic proteins. The histone deacetylase (HDAC) inhibitor chidamide can induce BIM expression, leading to apoptosis of lymphoma cells with good efficacy in refractory recurrent DLBCL. In this study, the synergistic mechanism of chidamide and venetoclax in DLBCL was determined through in vitro and in vivo models. We found that combination therapy significantly reduced the protein levels of MYC, TP53, and BCL2 in activated apoptotic-related pathways in DLBCL cells by increasing BIM levels and inducing cell apoptosis. Moreover, combination therapy regulated expression of multiple transcriptomes in DLBCL cells, involving apoptosis, cell cycle, phosphorylation, and other biological processes, and significantly inhibited tumor growth in DLBCL-bearing xenograft mice. Taken together, these findings verify the in vivo therapeutic potential of chidamide and venetoclax combination therapy in DLBCL, warranting pre-clinical trials for patients with DLBCL.


3美国杜克大学医学院,美国达勒姆,NC 27710
方法:利用生物信息学技术分析表观遗传学HDAC基因与BCL2基因之间的相关性;体外应用DHL细胞株DB(MYC/BCL2重排)和DEL细胞株SUDHL-4(MYCBCL2表达)分别进行单药和联合用药处理,通过CCK-8法检测细胞活力,流式细胞术检测细胞凋亡和周期,RNA测序和蛋白质印迹(western blot)检测MYCBCL2TP53等相关基因的mRNA水平及蛋白的表达;体内建立DLBCL异种移植小鼠模型进行单药和联合用药治疗,分析并评价药物治疗后皮下瘤的大小和病理切片。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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