凋亡蛋白抑制因子与阿克拉霉素诱导骨髓增生异常综合征细胞株细胞凋亡关系的体外研究  

Study on the Relationship Between the Inhibitors of Apoptosis Proteins and the Apoptosis of Myelodysplastic Syndrome Cell Line Cells Induced by Aclacinomycin in vitro

作　　者：林茂芳[1] 熊红[2] 蔡真[1] 王云贵[1] 

机构地区：[1]浙江大学医学院附属第一医院血液科,杭州310003 [2]第二军医大学长征医院血液科,上海200003

出　　处：《中国实验血液学杂志》2004年第5期606-609,共4页Journal of Experimental Hematology

摘　　要：为了探讨阿克拉霉素 (aclacinomycin ,ACM)诱导骨髓增生异常综合征 (MDS)细胞凋亡与凋亡蛋白抑制因子 (IAP)的关系 ,以DNA片段原位末端 (TUNEL)标记方法检测MDS细胞株MUTZ 1细胞 (RAEB型 )经ACM作用后的TUNEL阳性细胞 ,并用RT PCR技术检测cIAP1及cIAP2mRNA表达水平的变化。结果表明 :① 0 .2 5μmol LACM处理 2 4小时 ,MUTZ 1细胞cIAP1mRNA相对表达量 (cIAP1 GAPDH)为 0 .2 4± 0 .0 5 ,与未处理组(0 4 4± 0 0 8)相比 ,有显著的差异 (P =0 .0 2 4 ) ;0 .5 μmol L和 1.0 μmol LACM处理 2 4小时 ,cIAP1mRNA相对表达量分别为 0 .15± 0 .0 9和 0 .0 0± 0 .0 0 ,与未处理组相比 ,均有非常显著的差异 (P值分别为 0 .0 0 2和 0 .0 0 0 2 )。相关性分析显示 ,cIAP1mRNA表达强度与ACM作用浓度呈负相关 (r=- 0 .97,P <0 .0 1)。② 0 .5 μmol LACM作用 6、12、2 4小时 ,cIAP1mRNA相对表达量分别为 0 .95± 0 .0 4 ,0 .73± 0 .0 5 ,0 .38± 0 .0 7,与未经ACM处理组相比 ,均有显著的差异 (P值分别为 0 .0 2 ,0 .0 0 0 4 ,0 .0 0 0 2 )。相对表达量与ACM作用时间呈负相关 (r =- 0 996 ,P <0 0 1)。③ 0 .5 μmol LACM处理 3,6 ,12和 2 4小时 ,MUTZ - 1细胞cIAP2mRNA相对表达量分别为 1 17±0 .0 6 ,0 .To explore the correlation between the cellular inhibitors of apoptosis proteins (cIAPs) and the apoptosis of myelodysplastic syndrome (MDS ) cell line (RAEB type) cells induced by aclacinomycin (ACM), the apoptosis of MDS cell line MUTZ-1 cells induced by ACM was analyzed with terminal de oxyribonucleotidy transferase mediated dUTP-biotin nick end labeling (TUNEL) te c hnique. By using semi-quantitative reverse transcriptase polymerase chain react i on (RT-PCR), the expression levels of cIAP-1 and cIAP-2 mRNA in MUTZ-1 cells wer e assayed. The results showed as follow: (1) Using 0.5 μmol/L, 1.0 μmol/L ACM treated cells for 24 hours, the relative expression lev el of cIAP-1 mRNA(cIAP-1 / GAPDH ) was lower than those in the untreated cell group (P=0.002, 0.0002, respectively) . (2) Using 0.5 μmol/L ACM treated for 6, 12, 24 hours, the rela tive expre ssion level of cIAP-1 mRNA was 0.95±0.04, 0.73±0.05, 0.38±0.07, respectively and the relative expression level of cIAP-1 mRNA was correlated negatively wit h t he time treated by ACM (r =-0.996, P<0.01). (3) Using 0.5 μmol/L A CM treated for 3,6,12,24 hours, the relative expression level of cIAP-2 mRNA w as 1.17±0.06, 0.91±0.03, 0.69±0.07 and 0.00±0.00, respectively and relative expression level of CIAP-2 mRNA was correlated negati vely with the time treated by ACM (r=-0.091, P<0.01). (4) The percentag es of TU NEL postive cells were correlated negatively with the relative expression level of CIAP1 and CIAP2 mRNA (r=-0.984, -0.959 and P=0.002, 0.013 respectivel y) when treated with increasing concentration of ACM. In conclusion, ACM can induce significantly MUTZ-1 cell apoptos is via suppressing expression of anti-apoptotic gene cIAP-1 and cIAP-2 mR NA.

关 键 词：阿克拉霉素 骨髓增生异常综合征 凋亡蛋白抑制因子 细胞凋亡 

分 类 号：R733.3[医药卫生—肿瘤] R733.7[医药卫生—临床医学]