Yu Run-Hong, Zeng Li, Liu Yu-Feng
Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Xue Ye Xue Za Zhi. 2011 Jun;32(6):363-7.
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.
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).
(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. (3) 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 III.
(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-κBp65 expression of transplanted tumors, especially for their combination.
探讨去铁胺（DFO）及DFO联合三氧化二砷（ATO）对裸鼠人早幼粒白血病细胞株（HL-60）移植瘤生长的抑制作用及其机制。
将HL-60细胞皮下接种于裸鼠，建立HL-60细胞株裸鼠移植瘤模型。将荷瘤小鼠随机分为四组：50mg/kg DFO组（Ⅰ组）、3mg/kg ATO组（Ⅱ组）、联合组（50mg/kg DFO + 1.5mg/kg ATO，Ⅲ组）和生理盐水对照组。自接种当天起腹腔注射给药（每日1次，共10天）。比较各组对肿瘤生长的抑制作用。末次给药后24小时，采用免疫组化法检测肿瘤组织中核因子κB p65（NF-κBp65）表达水平。
（1）接种后第7～8天，所有裸鼠均可观察到肿瘤生长，直径0.5～1.0cm，随后迅速生长；（2）对照组、Ⅰ组、Ⅱ组和Ⅲ组肿瘤重量分别为（2.62±0.54）g、（2.55±0.82）g、（2.34±0.79）g和（1.95±0.39）g，Ⅰ组、Ⅱ组和Ⅲ组的生长抑制率分别为2.67%、10.69%和25.57%。DFO单独及联合ATO均能抑制移植瘤生长，联合组作用更明显，荷瘤小鼠重要脏器无损伤；（3）三个实验组NF-κBp65表达均值比较差异有统计学意义（P < 0.05），表达量由高到低依次为对照组>Ⅱ组>Ⅰ组>Ⅲ组。
（1）DFO和ATO对荷瘤小鼠均有抗肿瘤活性，二者联合应用效果明显；（2）DFO联合ATO在裸鼠中耐受性良好，无明显不良反应；（3）DFO和ATO均可下调移植瘤NF-κBp65表达，二者联合作用更显著。
