VPA联合HA14-1对Bcl-2高表达的BALL-1细胞作用的实验研究  

Effects of VPA in combination with HA14-1 on a Bcl-2 overexpressed leukemia cell line BALL-1

作　　者：薛红漫[1] 陈纯[1] 张建瑜[1] 张金华[1] 李文益[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：《中国病理生理杂志》2006年第11期2227-2230,共4页Chinese Journal of Pathophysiology

摘　　要：目的:观察体内外丙戊酸(VPA)和HA14-1联合应用对Bc l-2高表达的白血病细胞的杀伤效能。方法:(1)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、Bc l-2的平均荧光指数(MFI)以及胱冬肽酶(caspase)3、8和9的含量;(2)NOD/SC ID鼠在接种BALL-1后24 h按(1)分组进行实验。记录各组小鼠的存活时间;流式细胞仪检测各组小鼠外周血、骨髓、肝、肺、脾组织中CD19的表达。结果:(1)HA14-1+VPA组凋亡率高达(76.5±6.9)%,与另3组比较P<0.01。HA14-1组和联合作用组中Bc l-2低于其它两组,caspase 9和3的含量则较高,差异显著;联合作用组上述3种指标与其它组的差异更显著(P<0.01)。Caspase 8在各组间无显著差异。(2)HA14-1+VPA组小鼠生存(87.5±4.5)d,显著长于其它3组,而其它3组之间无明显差异。HA14-1+VPA组CD19在外周血、骨髓、肝、脾中的表达显著低于另3组。结论:HA14-1与VPA联合用药,可克服Bc l-2高表达造成的对VPA的抗性。AIM： To observe the effects of valproic acid （VPA） and HA14 - 1 on Bcl - 2 overexpressed leukemia cells in vitro and in vivo. METHODS： （ 1 ） Cells were divided into control group, HA14 - 1 group, VPA group and HA14- 1 ＋ VPA group. The apoptotic rate, the mean fluorescent index （MFI） of Bcl- 2, the levels of caspase 3, 8 and 9 were detected with FCM. （2） 24 h after transplantation with BALL - 1, the NOD/SCID mice were divided into 4 groups as （ 1 ） , then the survival time was compared. The expression of CD19 in the peripheral blood cells, bone marrows, livers, spleens and lungs of each group was detected. RESULTS： （ 1 ） The apoptotic rate in HA14 - 1 ＋ VPA group was （76.5 ±6.9） % , this was significantly elevated compared to the data in other groups （ P 〈 0. 01 ）. In HA14 - 1 group and combination group, there were lower Bcl - 2 and higher caspase 9 and caspase 3 levels, compared with other two groups. Between these two groups the above three index were also significant different （ P 〈 0. 01 ）. （2） The survival time of the combination group was （87.5 ±4. 5） days, significantly longer than that in any other groups. The expression of CD19 in detected organs in combination group was lower than that in control or single treatment group. CONCLUSION： Combination of HA14 - 1 with VPA can overcome resistence to VPA in leukemia cells of high Bcl - 2 level.

关 键 词：丙戊酸 HAl4-1 BCL-2 白血病 NOD/SCID鼠 

分 类 号：R363[医药卫生—病理学]