目的探讨纳米三硫化三砷(As2S2)与传统剂型As2S3对人骨髓增生异常综合征(MDS)细胞株MUTZ-1的生长抑制作用及其可能的机制。方法用MTT法比较两种剂型的As2S3对MUTZ-1细胞的生长抑制作用;透射电子显微镜技术分析细胞形态和超微结构的变化;流式细胞术分析细胞凋亡和周期的改变;发光比色法分析oaspase-3活性。结果2、4、8、16μmol/L两种剂型As2S3分别处理MUTZ-1细胞48h后,纳米As2S3对细胞的抑制率分别为48.9%、75.9%、89.4%和96.5%,而传统剂型As2S3组分别为14.5%、25.4%、34.7%和51.5%,曲组相比差异有统计学意义(P值均〈0.01);纳米As2S3组细胞凋亡率分别为(12.9±1.9)%、(19.2±2.2)%、(30.1±2.5)%和(45.9±2.3)%,而传统剂型As2S3组分别为(5.3±1.8)%、(11.1±2.6)%、(19.3±2.3)%和(25.5±2.5)%,两组相比差异也有统计学意义(P值均〈0.01);纳米As2S3组G2/M期细胞比例、caspase-3活性明显高于传统剂型As2S3组(P〈0.01),且以上各指标均呈浓度-时间依赖性。结论两种剂型As2S3对MUTZ-1细胞均有生长抑制和诱导凋亡作用,其机制可能与G2/M期细胞阻滞以及caspase-3活化有关;与传统剂型的As2S3相比,纳米As2S3有更强的抗肿瘤作用。
Objective To in vitro study the inhibition effect and possible mechanism of As2S3 nanop- articles( As2S3 nano) on human MDS cell line MUTZ-1 and to compare with that of traditional As2S3. Method MUTZ-1 cells were treated with As2S3 nano and tranditional regular-sized particles (TRSP) at different concentrations. The cell growth inhibition rate was determined by MTT assay, cell apoptosis by morpbplogy and flow cytometry (FCM) , cell cycle by FCM and the activity of caspase-3 by chemiluminescence assay. Results Treatment of As2S3 nano and TRSP at concentrations of 2, 4, 8 and 16 μmoL/L for 48 h could lead to a significant dose-dependent decrease of MUTZ-1 cells and induce apoptosis. The percentages of inhibition were 48.9% , 75.9% , 89.4% and 96.5% in As2S3 nano vs 14.5% , 25.4% , 34.7% and 51.5% in TRSP and apoptosis rates were (12.9±1.9)%,(19.2±2.2)%,(30. 1±2.5)% and (45.9±2.3)% inAs2S3 nanovs (5.3±1.8%)%,(11.1 ±2.6)%, (19.3±2.3)% and (25.5±2.5)% in TRSP respectively. There was statistically significant difference in these two groups( P 〈 0.01 ). The proportion of cell in G2/M phase and the activity of easpase-3 of MUTZ-1 cells treated with As2S3 nano were significantly higher than those treated with control group and As2 S3 TRSP groups ( P 〈 0.01 ). Conclusions As2 S3 nanoparticles and TRSP can inhibit the proliferation of MUTZ-1 cells and induce apoptosis, which maybe through activating caspase-3 pathways and increasing the proportion of G2/M phase. As2S3 nanoparticles can produce a much better antitter effect than As2S3 TRSP do.