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

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/...

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

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.