去铁胺单独及联合三氧化二砷对裸鼠HL-60细胞移植瘤的
抑制作用及其可能机制
于润红;曾利;刘玉峰
【期刊名称】《中华血液学杂志》 【年(卷),期】2011(032)006
【摘要】Objective To investigate the effect of deferoxamine( DFO) and DFO in combination with arsenic trioxide (ATO) on inhibition of HL-60 cells xenograft tumor growth in nude mice and its mechanism. Methods Xenograft tumor model of HL-60 cell line in nude mice was established by inoculating HL-60 cells subcutaneously into nude mice. The tumor-bearing mice were randomly divided into four groups: 50 mg/kg DFO group( group Ⅰ) , 3 mg/kg ATO group( group Ⅱ ) , combination group (50 mg/kg DFO +1.5 mg/kg ATO (group Ⅲ) and normal saline control group. The drugs were administered intraperitoneally from the day of inoculation (once a day for 10 days). The inhibitory effects on the tumor growth were compared. NF-κBp65 expression levels of the tumors were detected by immunohistochemistry (24h after the last administration) . Results ① Tumors growth could be observed in all of the nude mice on day 7 to day 8 after inoculation, 0.5 -1.0 cm in diameter, and then grew rapidly; ② Tumor weight of control group, group Ⅰ , group Ⅱ and group Ⅲ were ( 2.62±0.54)g, (2.55 ±0. 82)g, (2. 34 ±0. 79)g and (1.95 ±0.39) g respectively, and the growth inhibition rates in group Ⅰ ,
group Ⅱ and group Ⅲ were 2.67% , 10. 69% and 25.57% respectively. Both DFO alone and in combination with ATO could inhibit the growth of transplanted tumors, and the combination group exhibited more effects, with no vital organ damages in the tumor-bearing mice.③There was significant difference in mean value of NF-κBp65 expression among the three experimental groups(P<0.05) , with a descending order of control group > group Ⅱ , > group Ⅰ > group Ⅲ. Conclusion ① Both DFO and ATO have antitumor activities on tumor-bearing mice, and their combination has an obvious and significant effect. ②DFO combined with ATO, is well tolerated with no significant adverse effects in the nude mice. ③Both DFO and ATO can downregulate NF-κBp65 expression of transplanted tumors, especially for their combination.%目的 探讨去铁胺(DFO)单独及联合三氧化二砷(As2O3)对裸鼠HL-60白血病细胞移植瘤的抑制作用及机制,为临床采用铁螯合剂治疗或辅助治疗白血病提供实验依据.方法 用高致瘤性HL-60细胞建立裸鼠皮下移植瘤模型,随机分为4组:50 mg/kg DFO单药组、3 mg/kg As2O3单药组、联合用药组(50 mg/kg DFO+1.5 mg/kg As2O3)及生理盐水对照组;HL-60细胞接种当天即开始给药,均采用腹腔注射给药,每日注射1次,连续10 d;比较上述药物对裸鼠移植瘤的抑制作用,并对移植瘤组织NF-κBp65表达进行免疫组化检测(末次给药后24 h).结果 ①全部裸鼠于接种后第7～8天成瘤,出现肉眼可见的瘤块,直径0.5～1.0 cm,成瘤后瘤体生长迅速.②DFO单药组、As2O3单药组、联合用药组的移植瘤重量分别为(2.55±0.82)、(2.34±0.79)、(1.95±0.39)g,抑瘤率分别为2.67%、
10.69%、25.57%;生理盐水对照组的移植瘤重量为(2.62±0.54)g;DFO单药及DFO联合As2O3均能抑制移植瘤生长,其中以联合用药效果最好,且未引起重要脏器损害.③代表移植瘤组织NF-κBp65表达的吸光度(A)值:对照组>As2O3单药组>DFO单药组>DFO联合As2O3用药组,4组两两相互比较差异均有统计学意义(P值均<0.05).结论 ①采用高致瘤性HL-60细胞在裸鼠皮下接种,可成功建立移植瘤模型;②DFO和As2O3单药均对高致瘤HL-60细胞移植瘤裸鼠有抗瘤作用,二者联合作用显著;③荷瘤裸鼠对DFO联合As2O3应用能较好耐受,DFO可降低As2O3用量,促进其杀伤肿瘤作用,且可降低As2O3的不良反应;④DFO和As2O3均可降低移植瘤组织NF-κBp65的表达水平,二者联合作用更加明显.
【总页数】5页(363-367)
【关键词】去铁胺;砷剂;NF-κB;HL-60细胞;动物实验 【作者】于润红;曾利;刘玉峰
【作者单位】450052,郑州大学第一附属医院儿科;450052,郑州大学第一附属医院儿科;450052,郑州大学第一附属医院儿科 【正文语种】中文 【中图分类】 【文献来源】
https://www.zhangqiaokeyan.com/academic-journal-cn_chinese-journal-hematology_thesis/0201232773160.html 【相关文献】
1.硼替佐米或联合三氧化二砷治疗HL-60白血病细胞移植瘤裸鼠的实验研究 [J],
去铁胺单独及联合三氧化二砷对裸鼠HL-60细胞移植瘤的抑制作用及其
