丙戊酸联合HA14-1诱导Bcl-2高表达的白血病细胞株BALL-1凋亡  

Combined apoptotic inducing effects of VPA and HA14-1 on BALL-1:A leukemia cell line overexpression of Bcl-2

作　　者：薛红漫[1] 李文益[1] 孟哲[1] 李晓圆[1] 张金华[1] 

机构地区：[1]中山大学附属第二医院儿科,广东广州510120

出　　处：《中国实验诊断学》2006年第10期1173-1175,共3页Chinese Journal of Laboratory Diagnosis

摘　　要：目的观察体内外丙戊酸(VPA)和HA14-1联合应用对Bcl-2高表达的白血病细胞的杀伤效能及对外周血象的影响。方法(1)将BALL-1分为空白对照组1、mmol/L VPA组5、mmol/L VPA组、15 mmol/L VPA组,作用72 h,流式细胞仪检测各组细胞凋亡结果;(2)将BALL-1分为对照组、VPA组、HA14-1组、VPA+HA14-1组,作用后流式细胞法检测各组凋亡率;(3)每组6只NOD/SCID鼠在每只鼠接种1×107/0.2 ml BALL-1后24 h按如下分组进行实验:①对照组;②HA14-1组,经尾静脉注射灭菌HA14-1 25 mg.kg-1.d-1,共7天;③VPA组,注射灭菌VPA 250 mg.kg-1.d-1,共7天;④HA14-1+VPA组,注射灭菌HA14-1 25 mg.kg-1.d-1,4小时后再注射灭菌VPA 250 mg.kg-1.d-1,共7天。记录各组小鼠的存活时间。(4)将普通小白鼠共24只按(3)方法进行分组,比较几组普通小鼠的生存率、存活时间,及外周血细胞计数。结果(1)VPA15 mmol/L作用72 h BALL-1凋亡率为(24.8±2.8)%,与其它3组比较P<0.01;另3组之间比较P>0.05。(2)HA14-1组、VPA组凋亡率分别为(4.6±0.1)%(、4.8±0.5)%,与对照组比较,P>0.05。HA14-1+VPA组凋亡率高达(76.5±6.9)%,与另3组比较P<0.01。(3)HA14-1+VPA组小鼠生存天数为(87.5±4.5)天,显著长于其他3组,而其他3组之间无差异。(4)HA14-1单独作用组和HA14-1与VPA联合作用组表现为白细胞与血小板轻微而短期下降,而小鼠的生存率、存活时间无显著性差异。结论HA14-1与VPA联合用药,可克服Bcl-2高表达造成的对VPA的抗性。Objective To observe the joint effects of Valproic acid（VPA）and HAI4-1 on human leukemia cell line overexpression of Bcl-2 either in vitro or in vivo, and to observe the impact of them on the peripheral blood cells. Methods （ 1 ） BALL- 1 cell were divided into：control group, 1 mmol/L V＇PA group,5 mmol/L VPA group and 15 mmol/L VPA group,72 hours after treated, the apoptotic rate of cells was analyzed with the FCM. （2）Cells were divided into： control group, VPA group, HA14-1 group and VPA ± HAI4-1 group,and the apoptofic rate was analyzed with the FCM.（3）24 hrs after transplantation with 1 × 10^7/0.2 ml BALL-1 into each NOD/SCID monse,24 mice were divided into 4 study groups： control group; VPA group（VPA 250 mg· kg^- 1·d^- 1 was injected throngh tail vein for 7 days） ; HA14-1 group（HA14-1 25 mg· kg^- 1·d^- 1 was injected through tail vein for 7 days） ; and VPA ± HA14- 1 group（for 7 days, HA14-1 25 mg· kg^- 1·d^- 1 was injected first, in 4 hrs VPA 250 mg· kg^- 1·d^- 1 was given）. Then the survival time were compared. （4） To divide the common mice into the same 4 groups as NOD/SCID mice, Then to compare the survival rate, survival time and the count of the peripheral blood cells between groups. Results （ 1 ） The apoptotic rate of VPA 15 mmoL/L group was （24.8 ± 2.8） % ,higher than any other groups （ P 〈 0.01 ）, while there were no difference among the other three groups（ P 〉 0.05）. （2）The apoptotic rate of the HA14-1 group and the VPA group were（4.6 ± 0.1 ）% and（4.8 ± 0.5）%, there were no significant difference compared with the control group; but the data of the HA14-1 ＋ VPA group was significantly elevated to（76.5 ± 6.9）%, P 〈 0.01. （3）The survival time of the combination group was（87.5 ± 4.5）days,longer than any other groups, while there were no difference among other three groups. （4） For short term, leucocytes and plate.lets in HA14-1 group and combinated group showed lightly drop down. Conduslon Combinat

关 键 词：丙戊酸 HA14-1 BCL-2 白血病 NOD/SCID鼠 

分 类 号：R733.7[医药卫生—肿瘤]