中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2011年
6期
363-367
,共5页
去铁胺%砷剂%NF-κB%HL-60细胞%动物实验
去鐵胺%砷劑%NF-κB%HL-60細胞%動物實驗
거철알%신제%NF-κB%HL-60세포%동물실험
Deferoxamine%Arsenic trioxide%Nuclear factor-kappaB%Leukemia%Nude mice
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.
目的 探討去鐵胺(DFO)單獨及聯閤三氧化二砷(As2O3)對裸鼠HL-60白血病細胞移植瘤的抑製作用及機製,為臨床採用鐵螯閤劑治療或輔助治療白血病提供實驗依據.方法 用高緻瘤性HL-60細胞建立裸鼠皮下移植瘤模型,隨機分為4組:50 mg/kg DFO單藥組、3 mg/kg As2O3單藥組、聯閤用藥組(50 mg/kg DFO+1.5 mg/kg As2O3)及生理鹽水對照組;HL-60細胞接種噹天即開始給藥,均採用腹腔註射給藥,每日註射1次,連續10 d;比較上述藥物對裸鼠移植瘤的抑製作用,併對移植瘤組織NF-κBp65錶達進行免疫組化檢測(末次給藥後24 h).結果 ①全部裸鼠于接種後第7～8天成瘤,齣現肉眼可見的瘤塊,直徑0.5～1.0 cm,成瘤後瘤體生長迅速.②DFO單藥組、As2O3單藥組、聯閤用藥組的移植瘤重量分彆為(2.55±0.82)、(2.34±0.79)、(1.95±0.39)g,抑瘤率分彆為2.67%、10.69%、25.57%;生理鹽水對照組的移植瘤重量為(2.62±0.54)g;DFO單藥及DFO聯閤As2O3均能抑製移植瘤生長,其中以聯閤用藥效果最好,且未引起重要髒器損害.③代錶移植瘤組織NF-κBp65錶達的吸光度(A)值:對照組>As2O3單藥組>DFO單藥組>DFO聯閤As2O3用藥組,4組兩兩相互比較差異均有統計學意義(P值均<0.05).結論 ①採用高緻瘤性HL-60細胞在裸鼠皮下接種,可成功建立移植瘤模型;②DFO和As2O3單藥均對高緻瘤HL-60細胞移植瘤裸鼠有抗瘤作用,二者聯閤作用顯著;③荷瘤裸鼠對DFO聯閤As2O3應用能較好耐受,DFO可降低As2O3用量,促進其殺傷腫瘤作用,且可降低As2O3的不良反應;④DFO和As2O3均可降低移植瘤組織NF-κBp65的錶達水平,二者聯閤作用更加明顯.
목적 탐토거철알(DFO)단독급연합삼양화이신(As2O3)대라서HL-60백혈병세포이식류적억제작용급궤제,위림상채용철오합제치료혹보조치료백혈병제공실험의거.방법 용고치류성HL-60세포건립라서피하이식류모형,수궤분위4조:50 mg/kg DFO단약조、3 mg/kg As2O3단약조、연합용약조(50 mg/kg DFO+1.5 mg/kg As2O3)급생리염수대조조;HL-60세포접충당천즉개시급약,균채용복강주사급약,매일주사1차,련속10 d;비교상술약물대라서이식류적억제작용,병대이식류조직NF-κBp65표체진행면역조화검측(말차급약후24 h).결과 ①전부라서우접충후제7～8천성류,출현육안가견적류괴,직경0.5～1.0 cm,성류후류체생장신속.②DFO단약조、As2O3단약조、연합용약조적이식류중량분별위(2.55±0.82)、(2.34±0.79)、(1.95±0.39)g,억류솔분별위2.67%、10.69%、25.57%;생리염수대조조적이식류중량위(2.62±0.54)g;DFO단약급DFO연합As2O3균능억제이식류생장,기중이연합용약효과최호,차미인기중요장기손해.③대표이식류조직NF-κBp65표체적흡광도(A)치:대조조>As2O3단약조>DFO단약조>DFO연합As2O3용약조,4조량량상호비교차이균유통계학의의(P치균<0.05).결론 ①채용고치류성HL-60세포재라서피하접충,가성공건립이식류모형;②DFO화As2O3단약균대고치류HL-60세포이식류라서유항류작용,이자연합작용현저;③하류라서대DFO연합As2O3응용능교호내수,DFO가강저As2O3용량,촉진기살상종류작용,차가강저As2O3적불량반응;④DFO화As2O3균가강저이식류조직NF-κBp65적표체수평,이자연합작용경가명현.
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.
