三氧化二砷对慢性髓系白血病细胞周期及Survivin表达的影响

Arsenic trioxide inducing G_2/M cell cycle arrest and the expression of Survivin in chronic myeloid leukemic cells

目的 研究三氧化二砷 (As2 O3 )对慢性髓系白血病细胞 (K5 62 )的作用特点及其机制。方法 不同浓度As2 O3 作用于K5 62细胞后 ,四唑盐 (MTT)比色法分析细胞增殖 ;流式细胞术检测细胞周期分布、细胞凋亡及Survivin抗原表达 ;RT PCR检测SurvivinmRNA的表达。结果 2～ 10 μmol/L的As2 O3 能有效抑制K5 62细胞增殖 ,但未能诱导明显的细胞凋亡。周期分析显示 ,G2 /M期细胞比例显著增多 ;同时G2 /M细胞周期依赖性表达的SurvivinmRNA和蛋白表达增加。结论 As2 O3 明显抑制K5 62细胞的生长 ,其机制是诱导G2 /M期细胞周期停滞。Survivin表达上调可能是K5 62细胞对As2O3诱导凋亡抵抗的机制之一。

Objective To explore the characteristic and m ec hanism of arsenic trioxide (As 2O 3) on chronic myeloid leukemic cells (K562).Methods After K562 cells were treated with As 2O 3 of various concentrations,cell proliferation was tested by MTT assay,the distribution of c ell cycles,cell apoptosis and the expression of Survivin antigen were detected b y flow cytometry,and the content of expression of survivin gene was determined b y RT-PCR.Results As 2O 3(2～10μmol/L) inhibited K562 cells growth eff ectively,but could not induce significant cell apoptosis.The percentage of K562 cells at G 2/M phase increased,and the expression of Survivin mRNA and protein was up-regulated after the treatment.Conclusion As 2O 3 inhibited the growth of K562 cells by indu cing them arrest at G 2/M cell cycle.The up-regulation of Survivin expression might be one of the possible mechanisms of their resistance to As 2O 3 inducin g cell apoptosis.