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On-line Access: 2022-08-12
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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,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200016 @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", %0 Journal Article TY - JOUR
组蛋白去乙酰化酶(HDAC)抑制剂西达本胺联合维奈托克通过下调MYC、BCL2和TP53的表达协同抑制弥漫性大B细胞淋巴瘤的生长1南昌大学第二附属医院血液科,中国南昌,330006 2江西省血液重点实验室,中国南昌,330006 3美国杜克大学医学院,美国达勒姆,NC 27710 目的:探讨表观遗传学组蛋白去乙酰化酶(HDAC)抑制剂西达本胺与BCL2抑制剂维奈托克的联合对弥漫性大B细胞淋巴瘤(DLBCL)生长的影响及相关机制。 创新点:本研究首次探索了将西达本胺和维奈托克联合作用于MYC+/BCL2+DLBCL,使用二代测序(NGS)开创性地从表观遗传学和基因蛋白层面探讨这种联合用药的效果及作用机制。 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(MYC、BCL2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MYC、BCL2、TP53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。 结论:西达本胺与维奈托克协同抑制DLBCL的生长,通过调控表观遗传的改变,沉默MYC、TP53的表达,降低抗凋亡蛋白BCL2表达以及增加促凋亡蛋白BIM表达,诱导肿瘤细胞的凋亡和细胞周期阻滞。 关键词组: Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article
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