State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, School of Basic Medical Science, Guizhou Medical University, Guiyang 550004, China.
Exp Oncol. 2022 Aug;44(2):126-131. doi: 10.32471/exp-oncology.2312-8852.vol-44-no-2.17983.
Histone deacetylases, especially zinc-dependent deacetylases HDACs, are among attractive drug targets for treating cancer in recent years.
To explore the expression level of HDACs in several human cancer cell lines and examine the possible association between their expression and the sensitivity/resistance to the selective- or pan-HDAC inhibitors.
The RNA expression of 11 HDACs isoforms was assayed in HeLa, HepG2, AV3, HEK293, A549, and K562 cells by semiquantitative reverse transcription-polymerase chain reaction. The sensitivity/resistance of these cell lines to the pan- or selective- HDAC inhibitors was estimated by MTS assay.
The relative transcription of HDACs genes demonstrated that members of Class I HDAC (HDAC1, 2 and 3) and members of Class II HDAC (HDAC4, 5, 6 and 7) had slight to significant levels of expression in cell lines under study with no dominant HDAC-subtype gene transcription. pan-HDAC inhibitor demonstrated superior antitumor activity compared to HDAC isoform-selective inhibitor.
The absence of the dominant HDAC-subtype gene transcription in different human cancer cell lines explains the inferior efficacy of HDAC isoform-selective inhibitors as compared to pan-HDAC inhibitors.
近年来，组蛋白去乙酰化酶（HDACs），尤其是锌依赖性去乙酰化酶（HDACs），成为治疗癌症的有吸引力的药物靶点之一。
探索几种人癌细胞系中 HDACs 的表达水平，并研究其表达与选择性或泛 HDAC 抑制剂敏感性/耐药性之间的可能关联。
通过半定量逆转录聚合酶链反应检测 HeLa、HepG2、AV3、HEK293、A549 和 K562 细胞中 11 种 HDACs 亚型的 RNA 表达。通过 MTS 测定评估这些细胞系对泛或选择性 HDAC 抑制剂的敏感性/耐药性。
HDACs 基因的相对转录表明，I 类 HDAC（HDAC1、2 和 3）和 II 类 HDAC（HDAC4、5、6 和 7）的成员在研究中的细胞系中表现出轻微至显著的表达水平，没有优势的 HDAC 亚型基因转录。与 HDAC 亚型选择性抑制剂相比，泛 HDAC 抑制剂表现出更好的抗肿瘤活性。
不同人癌细胞系中没有优势的 HDAC 亚型基因转录，这解释了与泛 HDAC 抑制剂相比，HDAC 亚型选择性抑制剂的疗效较差。
