三氧化二砷联合长春瑞滨、多西他赛对神经母细胞瘤SK-N-SH细胞系杀伤作用和细胞周期的影响

Effects of arsenic trioxide,vinorelbine and docetaxel on the cytotoxicity and cell cycle distribution in human SK-N-SH neuroblastoma cell line

目的观察三氧化二砷(As_2O_3)、长春瑞滨(vinorelbine)、多西他赛(docetaxel)对神经母细胞瘤SK-N-SH细胞系的杀伤作用和细胞周期的影响,为临床寻找新的治疗手段及合理用药提供依据。方法采用流式细胞术检测经过As_2O_3、vinorelbine或docetaxel作用后SK-N-SH细胞的凋亡率和细胞周期分布的变化,探讨它们对SK-N-SH细胞的杀伤作用和细胞周期的影响。结果As_2O_3作用48h、72h、96h和120h时SK-N-SH细胞的凋亡率分别为(10.91±2.27)%、(23.85±5.52)%、(36.61±14.75)%、(52.93±2.47)%;As_2O_3可使SK-N-SH细胞周期阻滞在G2/M,作用48h时处于G2/M期阻滞的细胞比例最高(26.54%±5.67%);Vinorelbine和docetaxel对SK-N-SH细胞具有杀伤作用,它们各自作用于SK-N-SH细胞的IC50分别为35nmol/L和90nmol/L;以不同浓度的vinorelbine或docetaxel作用于SK-N-SHI细胞48h,随着G2/M期阻滞的比例增高,SK-N-SH细胞的凋亡率随之升高。结论 As_2O_3对SK-N-SH细胞的杀伤作用具有时间依赖性,As_2O_3可使SK-N-SH细胞周期阻滞在G2/M期。Vinorelbine和docetaxel对SK-N-SH细胞的杀伤作用和G2/M期阻滞有关,属于G2/M期特异性杀伤药物。

Objective To vestigate the cytotoxicity and cell cycle distribution in human SK-N-SH neuroblastoma cell line treated with arsenic trioxide, vinorelbine or docetaxel, to explore new treatments and provide rational evidence for drugs therapy. Methods We explored the ability of arsenic trioxide, vinorelbine or docetaxel to induce neuroblastoma cells apoptosis and change cell cycle distribution by flow cytometry. Results After treatment with arsenic trioxide for 48h, 72h, 96h, and 120h, the apoptosis rates were （10.91 ±2.27）%, （23.85 ±5.52）%, （36.61 ±14.75）%, and （52.93 ±2.47）%, respectively. Arsenic trioxide could arrest cell cycle in G2/M phase. The percentage of G2/M phase （26.54 ± 5.67 ） % reached its highest proportion when treated with arsenic trioxide for 48h. The IC50 value of vinorelbine and doeetaxel on SK-N-SH cells were 35nmol/L and 90nmol/L, respectively.Vinorelbine and docetaxel at different concentrations for 48h have cytotoxicity effects on SK-N-SH cells, and with the increased proportion of G2/M cell cycle arrest, the apoptosis rates on SK-N-SH cells increased significantly. Conclusions The in vitro study showed arsenic trioxide induced SK-N-SH cells cytotoxity in a time-dependent manner, and arrested cell cycle in G2/M phase. Vinorelbine and docetaxel could induce SK-N-SH cells cytotoxity and arrest cell cycle in G2/M phase, which belongs to G2/M phase specific agents.