三氧化二砷对HL-60细胞和人白血病裸鼠移植瘤模型的作用

Effect of arsenic trioxide on HL-60 cells and HL-60 cell xenograft in nude mice

目的:探讨三氧化二砷(As2O3)对HL-60细胞增殖和凋亡的影响及其对HL-60细胞皮下移植瘤裸鼠的抗瘤作用和药物毒性。方法:不同浓度的As2O3处理HL-60细胞24h,采用MTT比色法检测细胞增殖活性,Hochest33342染色、DNA凝胶电泳、流式细胞仪检测细胞凋亡。建立皮下移植瘤裸鼠模型,随机分入对照组和As2O3组,比较两组的抑瘤作用和裸鼠一般状态的变化。结果:As2O3可有效抑制HL-60细胞增殖并诱导其凋亡,其中在5～50!mol/L浓度范围内表现出明显的剂量依赖性抑制效应。同时可显著抑制HL-60细胞皮下移植瘤的生长,并延长荷瘤裸鼠的生存时间,对裸鼠一般状况和体重无不良影响。结论:As2O3在体外和体内均可显著抑制HL-60细胞的增殖并诱导其凋亡,且无明显毒副作用。

Objective To assess the effect of arsenic trioxide on proliferation and apoptosis of HL-60 cells. And to investigate it＇s antitumor efficacy and adverse effects for HL-60-bearing nude mice. Methods HL-60 cells were treated with arsenic trioxide for 48 h and the cell proliferation was analyzed with MTT assay and cell apoptosis detected by Hoehest 33342 staining, DNA gel eleetrophoresis, fluorescence microscopy and flow eytometry, Nude mice bearing HL-60 cell xenografts were randomized into 2 groups to receive treatment with normal saline and arsenic trioxide. The tumor growth inhibition and general condition of the nude mice were observed. Results Arsenic trioxide could effectively inhibit HL-60 cell proliferation and induce cell apoptosis. At the concentrations of 5 μmol/L to 50 μmol/L, it had conspicuous dose- dependent effect. It also could inhibit the growth of the transplanted tumors and prolong the survival of nude mice. The administration was well tolerated by the mice. Conclusion Arsenic trioxide can significantly inhibit HL-60 cell proliferation and induce cell apoptosis Both in vitro and in vivo, and there are no significant adverse effects.