儿童急性淋巴细胞白血病细胞化疗耐药机制的探讨  

Study on drug resistance in pediatric leukemia

作　　者：胡群[1] 丁玉峰[1] 刘爱国[1] 张柳清[1] 周木想[1] 宋宇[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院,湖北武汉430030 [2]武汉市第一医院,湖北武汉430022

出　　处：《中国医院药学杂志》2005年第9期796-798,共3页Chinese Journal of Hospital Pharmacy

基　　金：国家自然基金资助项目(编号:39970778)

摘　　要：目的:探讨儿童急性淋巴细胞白血病(ALL)化疗耐药的机制。方法:将MDM2质粒转染进入儿童急性淋巴细胞白血病细胞系EU-4细胞,用免疫印迹法检测P65的表达,用四甲基偶氮唑盐(MTT)法检测转染后白血病细胞对阿霉素(ADM)的反应,并用流式细胞术检测转染前后白血病细胞周期的变化。结果:MDM2的转染能上调P65的表达,该作用是P53不依赖性的。同时观察到稳定转染MDM2的细胞表现出对ADM的耐药,细胞周期的测定也表明MDM2转染后亚G1期细胞明显减少(P<0.01),表明MDM2的转染抑制了白血病细胞凋亡(P<0.01)。结论:在P53缺乏时,MDM2作为一个转录因子直接激活P65的表达,从而发挥其抗凋亡的效应,揭示了肿瘤细胞化疗耐药的新机制。OBJECTIVE To determine the mechanism of drug resistance in pediatric leukemia. METHODS MDM2 was transfected to acute lymphoblastic leukemia（ALL） line EU-4 cell which lacks P53 expression and expressing very low levels of MDM2. RESULTS MDM2 up-regulated P65 expression in protein level. The effect of adriamycin（ADM） on MDM2-transfected EU-4 cell was detected by MTT assay. It showed that MDM2 transfection increased drug resistance of EU-4 cells to ADM compared with parent cells, and increased the apoptosis of EU-4 cells by flow cytometry. CONCLUSION MDM2 up-regulated P65 expression. MDM2 increased drug resistance of EU-4 cells to ADM. MDM2 elevated apoptosis of leukemia cells.

关 键 词：儿童白血病 化疗耐药 MDM2 

分 类 号：R963[医药卫生—微生物与生化药学]