Department of Hematology, Cancer Hospital of Shanxi Province, Taiyuan, Shanxi 030013, P.R. China.
Department of Biochemistry and Molecular Biology, Key Laboratory of Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11947. Epub 2021 Mar 2.
Diffuse large B‑cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism. The results demonstrated that chidamide induced the death of these cells in a concentration‑(0‑30 µmol/l) and time‑dependent (24‑72 h) manner, as determined using the Cell Counting Kit‑8 cell viability assay. Moreover, chidamide promoted cellular apoptosis, which was identified via flow cytometry and western blot analysis, with an increase in cleaved caspase‑3 expression and a decrease in Bcl‑2 expression. Chidamide treatment also decreased the expression level of STAT3 and its phosphorylation, which was accompanied by the downregulation of a class‑I histone deacetylase (HDAC) inhibitor, chidamide. Collectively, these data suggested that chidamide can be a potent therapeutic agent to treat DLBCL by inducing the apoptotic death of DLBCL cells by inhibiting the HDACs/STAT3/Bcl‑2 pathway.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种高度异质性的恶性肿瘤类型，表观遗传修饰（如乙酰化或去乙酰化）在其发生发展中发挥着重要作用。 西达本胺是一种新型组蛋白去乙酰化酶抑制剂，对多种类型的癌症具有抗癌作用。本研究旨在评估西达本胺对多种 DLBCL 细胞系的细胞效应，并探讨其潜在机制。结果表明，细胞计数试剂盒（CCK-8）细胞活力测定法检测结果显示，西达本胺以浓度（0-30 μmol/L）和时间（24-72 h）依赖性方式诱导这些细胞死亡。此外，西达本胺通过流式细胞术和 Western blot 分析促进细胞凋亡，表现为 cleaved caspase-3 表达增加和 Bcl-2 表达减少。西达本胺处理还降低了 STAT3 及其磷酸化的表达水平，同时伴有 I 类组蛋白去乙酰化酶（HDAC）抑制剂西达本胺的下调。综上所述，这些数据表明，西达本胺通过抑制 HDACs/STAT3/Bcl-2 通路诱导 DLBCL 细胞凋亡死亡，可作为治疗 DLBCL 的有效治疗药物。
