Synergistic anticancer effect of a combination of chidamide and etoposide against NK/T cell lymphoma
Synergistic anticancer effect of a combination of chidamide and etoposide against NK/T cell lymphoma
复制标题
DOI：
10.1002/hon.2954
复制
发表时间：
2021-12
影响因子：
3.3
通讯作者：
Wenting Song;Zhanjuan Chen;C. Shi;Yuyang Gao;Xiao-yan Feng;Hongwen Li;Zhaoming Li;Mingzhi Zhang
中科院分区：
文献类型：
--
作者：
Wenting Song;Zhanjuan Chen;C. Shi;Yuyang Gao;Xiao-yan Feng;Hongwen Li;Zhaoming Li;Mingzhi Zhang
自然杀伤/T细胞淋巴瘤（NKTCL）是一种高度侵袭性的血液恶性肿瘤。然而，目前对于难治性/复发患者的治疗尚未达成共识。在这项研究中，我们研究了组蛋白脱乙酰酶 (HDAC) 抑制剂西达本胺和 DNA 损伤剂依托泊苷在 NKTCL 中联合使用的协同抗癌作用和潜在机制。我们证明，单独使用西达本胺或依托泊苷可剂量和时间依赖性地抑制 NKTCL 细胞系 YT、NKYS 和 KHYG-1 的细胞活力。功能实验表明，西达本胺和依托泊苷联合治疗在体外和体内发挥协同抗增殖作用并增强细胞凋亡。此外，我们还检测了 DNA 损伤相关蛋白的表达，并检查了组蛋白乙酰化、细胞周期进程和线粒体膜电位 (MMP) 的变化。结果表明，组蛋白乙酰化增加、细胞周期停滞在 G2/M 期和 MMP 丧失，最终导致更大的 DNA 损伤，可能是西达本胺和依托泊苷组合在 NKTCL 中产生协同作用的原因。总而言之，我们的研究为联合 HDAC 抑制剂和 DNA 损伤剂治疗 NKTCL 的可能应用提供了证据。
Natural killer/T cell lymphoma (NKTCL) is a highly aggressive hematological malignancy. However, there is currently no consensus on therapies for refractory/relapsed patients. In this study, we investigated the synergistic anticancer effect and potential mechanism of combining chidamide, a histone deacetylases (HDACs) inhibitor, and etoposide, a DNA‐damaging agent, in NKTCL. We demonstrated that chidamide or etoposide alone dose‐ and time‐dependently inhibited the cell viability of NKTCL cell lines, YT, NKYS and KHYG‐1. Functional experiments suggested that combined chidamide and etoposide treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic death in vitro and in vivo. Furthermore, the expression of DNA damage related proteins was detected and we also examined the alternations in histone acetylation, cell cycle progression, and mitochondrial membrane potential (MMP). The results suggested that increased histone acetylation, cell cycle arrest at the G2/M phase and loss of MMP, converging to greater DNA damage, might account for the synergism of the combination of chidamide and etoposide in NKTCL. Taken together, our study provides an evident for possible application on combining HDACs inhibitors and DNA‐damaging agents for the treatment of NKTCL.