Shi Pengcheng, Zhang Leisi, Chen Kai, Jiang Zhiwu, Deng Manman, Zha Jie, Guo Xutao, Li Peng, Xu Bing
Department of Hematology, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, China.
Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology & Regenerative Medicine, Guangzhou Institutes of Biomedicine & Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Pharmacogenomics. 2017 Aug;18(13):1259-1270. doi: 10.2217/pgs-2017-0061. Epub 2017 Jul 26.
To investigate the combined action of decitabine (DAC) with chidamide (CS055) on acute lymphoblastic leukemia (ALL) cells.
MATERIALS & METHODS: ALL cell lines as well as primary cells from 17 ALL patients were subjected to different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow cytometry and western blot were employed to determine IC, apoptosis and checkpoint kinase 1 and γH2A.X expression.
Low-dose DAC combined with CS055 could effectively kill ALL cells by the reduction of cell viability and induction of apoptosis. This was also observed in primary cells from 17 ALL patients, especially for those with p16 gene deletion. Suppression of checkpoint kinase 1 phosphorylation and upregulation of γH2A.X expression was demonstrated to participate in DAC plus CS055-induced apoptosis.
Low-dose DAC could enhance chidamide-induced apoptosis in adult ALL, especially for patients with p16 gene deletion through DNA damage.
研究地西他滨（DAC）与西达本胺（CS055）对急性淋巴细胞白血病（ALL）细胞的联合作用。
对ALL细胞系以及17例ALL患者的原代细胞进行不同处理，然后采用细胞计数试剂盒-8（CCK-8）检测、流式细胞术和蛋白质免疫印迹法来测定IC、细胞凋亡以及检查点激酶1和γH2A.X的表达。
低剂量DAC联合CS055可通过降低细胞活力和诱导细胞凋亡有效杀伤ALL细胞。在17例ALL患者的原代细胞中也观察到了这一现象，尤其是那些存在p16基因缺失的患者。研究表明，抑制检查点激酶1磷酸化和上调γH2A.X表达参与了DAC加CS055诱导的细胞凋亡。
低剂量DAC可增强西达本胺诱导的成人ALL细胞凋亡，尤其是对于存在p16基因缺失的患者，其作用机制是通过DNA损伤实现的。
