Ibrutinib combined with low‐dose histone deacetylases inhibitor chidamide synergistically enhances the anti‐tumor effect in B‐cell lymphoma
Ibrutinib combined with low‐dose histone deacetylases inhibitor chidamide synergistically enhances the anti‐tumor effect in B‐cell lymphoma
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依鲁替尼联合低剂量组蛋白脱乙酰酶抑制剂西达本胺协同增强B细胞淋巴瘤的抗肿瘤作用
DOI：
10.1002/hon.3056
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发表时间：
2022-08
期刊：
影响因子：
--
通讯作者：
Jun Zhu
中科院分区：
文献类型：
--
作者：
Hui Yu;Lan Mi;Weimin Zhang;Yingying Ye;Miaomiao Li;Dingyao Hu;Jiaowu Cao;Dedao Wang;Xiaogan Wang;Ning Ding;Yuqin Song;Jun Zhu
组蛋白去乙酰化酶（HDAC）的异常活性经常在B细胞淋巴瘤中检测到，这表明HDAC抑制剂对B细胞恶性肿瘤的治疗意义。我们发现HDAC抑制剂处理的淋巴瘤细胞呈现布鲁顿酪氨酸激酶（BTK）的激活，其在B细胞恶性肿瘤的发展中起重要作用。因此，我们的研究旨在探索在西达米特（HDAC抑制剂）中加入伊克替尼（BTK抑制剂）是否可以在B细胞淋巴瘤中产生联合抗肿瘤作用。通过细胞活力测定、细胞周期和凋亡试剂盒，我们证明了伊曲替尼和西达米特在抑制肿瘤细胞增殖和运动方面具有明显的协同作用。与体外数据一致，在多种荷瘤小鼠模型中也观察到协同抗肿瘤作用。通过对肿瘤组织进行RNA-seq和流式细胞术，观察到西达米特和伊曲替尼联合治疗的抗肿瘤免疫增强。总之，这些机制的见解表明，同时靶向BTK和HDAC可能是B细胞淋巴瘤的有希望的临床治疗。
Aberrant activity of histone deacetylases (HDACs) is frequently detected in B-cell lymphomas, which indicated the therapeutic implications of HDAC inhibitors for B-cell malignancies. We have discovered that lymphoma cells treated with HDAC inhibitor presented with activation of Bruton tyrosine kinase (BTK) which played an important role in the development of B-cell malignancies. Therefore, our study intended to explore whether the addition of ibrutinib (BTK inhibitor) to chidamide (HDAC inhibitor) could generate combined anti-tumor effects in B-cell lymphomas. Using cell viability assay, cell cycle and apoptosis kit, we demonstrated an evident synergistic action of ibrutinib and chidamide in inhibiting tumor cell proliferation and motility. Consistent with in vitro data, the synergistic anti-tumor effects were also observed in multiple tumor-bearing mice models. By performing RNA-seq and flow cytometry of tumor tissue, the enhancement of anti-tumor immunity was observed with the co-treatment of chidamide and ibrutinib. Together, these mechanistic insights indicated that simultaneously targeting BTK and HDAC could be a promising clinical therapy for B-cell lymphomas.
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影响因子：
11.4
作者：
Kondo K;Shaim H;Thompson PA;Burger JA;Keating M;Estrov Z;Harris D;Kim E;Ferrajoli A;Daher M;Basar R;Muftuoglu M;Imahashi N;Alsuliman A;Sobieski C;Gokdemir E;Wierda W;Jain N;Liu E;Shpall EJ;Rezvani K
通讯作者：
Rezvani K
EZH2 抑制剂 SHR2554 和 HDAC 抑制剂西达本胺通过 ORC1 减少弥漫性大 B 细胞淋巴瘤 DNA 复制过程的协同抗肿瘤活性
影响因子：
5.2
作者：
Wang X;Wang D;Ding N;Mi L;Yu H;Wu M;Feng F;Hu L;Zhang Y;Zhong C;Ye Y;Li J;Fang W;Shi Y;Deng L;Ying Z;Song Y;Zhu J
通讯作者：
Zhu J
影响因子：
158.5
作者：
Tam, Constantine S.;Anderson, Mary Ann;Roberts, Andrew W.
通讯作者：
Roberts, Andrew W.
影响因子：
6.4
作者：
Fan, Fuli;Yoo, Hyeon Joo;Sellner, Leopold
通讯作者：
Sellner, Leopold
影响因子：
254.7
作者：
Teras, Lauren R.;DeSantis, Carol E.;Flowers, Christopher R.
通讯作者：
Flowers, Christopher R.