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  

The inhibition effect of DFO alone and in combination with ATO on xenograft tumor growth of HL-60 cells in nude mice and its possible mechanism

作　　者：于润红[1] 曾利[1] 刘玉峰[1] 

机构地区：[1]郑州大学第一附属医院儿科,450052

出　　处：《中华血液学杂志》2011年第6期363-367,共5页Chinese Journal of Hematology

摘　　要：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：50mg／kgDFO单药组、3mg／kgAs203单药组、联合用药组（50mg／kg DFO＋1．5mg／kgAs2O3）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13注射1次，连续10d；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24h）。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0．5～1．0cm，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。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- KBp65 expression levels of the tumors were detected by immunohistochemistry （24h after the last administra- tion）. 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 em in diameter, and then grew rapidly ; （1） 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）gand （1.95±0.39） grespectively, and the growth inhibition rates in group Ⅰ, group Ⅱ and group Ⅲwere 2.67% , 10.69% and 25.57% respectively. Both DFO alone arid 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-bearlng mice. （1）There 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 m. Conclusion （1） Both DFO and ATO have antitumor activities on tumor-bearing mice, and their combination has an obvious and significant effect. （2）DFO combined with ATO, is well tolerated with no significant adverse effects in the nude mice. （3）Both DFO and ATO can downregulate NF-KBp65 expression of transplanted

关 键 词：去铁胺 砷剂 NF-κKB HL-60细胞 动物实验 

分 类 号：R965[医药卫生—药理学]