新维甲酸类药物SX-116对急性早幼粒细胞白血病细胞系NB4的诱导凋亡作用

New Retinoid SX-116 Induces Apoptosis of Acute Promyelocytic Leukemia Cell Line NB4

本研究通过应用细胞增殖、形态学变化、细胞周期动力学、DNA电泳和RT PCR等方法 ,观察新维甲酸类化合物SX 116对急性早幼粒细胞白血病细胞系NB4的作用。研究结果发现SX 116在 10 -6 mol L浓度条件下能引起NB4细胞凋亡 ,凋亡相关基因bcl 2在药物作用 6小时表达减弱 ,随着作用时间延长其表达量又回升至原有水平 ;另一凋亡相关基因 p5 3在药物作用过程中表达无变化。新维甲酸类化合物SX

In this research, the effect of novel retinoid SX-116 on acute promyelocytic leukemia cell line NB4 was studied in vitro. Cell proliferation, cell morphological characters, flow cytometry, DNA electrophoresis and RT-PCR were observational parameters. The results showed that treated with SX-116 at 10 -6 mol/L, the growth and survival of NB4 cells were markedly inhibited, morphological changes of apoptosis, including membrane blebbing, chromosome condensation and fragmentation of nuclei were observed in NB4 cells after 24 hours exposure of SX-116. Further studies showed 'DNA ladder' in genomic DNA electrophoresis, as well as a typical apoptotic peak below G 1 phase presented in flow cytometry. The expression of apoptosis-related gene bcl-2 and p53 were examined. The level of bcl-2 mRNA was downregulated by 6-hour treatment of SX-116, while the gene restored to the normal level by following 12-, 24- and 48-hour exposure. However, p53 mRNA was unchanged during the treatment. The results demonstrated that SX-116 could induce apoptosis of NB4 cells while the mechanism remains to be studied.