重组人PDCD5蛋白对U937细胞化疗的增敏作用及机制  

Sensitizing Effect of Recombinant Human PDCD5 Protein on Chemotherapy of Acute Monocytic Leukemia Cell Line U937 and Its Mechanism

作　　者：王艳芳[1] 宋泉声[2] 张颖妹[2] 马大龙[2] 王应[2] 克晓燕[1] 

机构地区：[1]北京大学第三医院血液科,北京100191 [2]北京大学医学部免疫系人类疾病基因研究中心,北京100191

出　　处：《中国实验血液学杂志》2010年第2期277-281,共5页Journal of Experimental Hematology

摘　　要：本研究探讨重组人PDCD5(rhPDCD5)蛋白对U937血液肿瘤细胞化疗增敏作用的机制。利用流式细胞术检测rhPDCD5蛋白对化疗药诱导的细胞凋亡以及细胞周期的影响;用Hochest33258荧光染色观察细胞凋亡的形态变化;用caspase-3荧光活性检测分析rhPDCD5蛋白诱导凋亡的可能机制;用RT-PCR检测rhPDCD5蛋白对耐药基因表达的影响。结果表明:rhPDCD5蛋白可以通过caspase-3相关的途径促进化疗药诱导的U937细胞凋亡,增强化疗药对细胞周期的阻滞作用。另外,rhPDCD5蛋白也能通过减少耐药基因的表达而增强肿瘤细胞对化疗药的敏感性。结论:rhPDCD5蛋白的作用机制比较复杂,它可能通过促进凋亡、影响细胞周期、逆转耐药等途径发挥化疗增敏作用。This study was aimed to investigate the sensitizing ettect of recombinant human PDCD5 （rmPDCD3） protein on chemotherapy of U937 cell line and its mechanism. The flow cytometry was performed to assess the changes of cell apoptosis and cell cycle influenced by rhPDCD5. Hochest 33258 staining was used to observe morphology of the apoptotic cells. The activity change of caspase-3 was detected to analyse the possible mechanisms of rhPDCD5-induced apoptosis. RT-PCR was performed to observe the expression level of drug-resistant genes. The results showed that the percentage of apoptotic cells and the activity of caspase-3 remarkably increased in U937 cells treated with rhPDCD5 combined with chemotherapeutic drug; the cell cycle arrest induced by anti-tumor drug was also enhanced when combined with rhPDCD5 ; meanwhile, the expression levels of drug-resistant genes were down-regulated in jointly treated U937 cells. It is concluded that the chemosensitizing mechanisms of rhPDCD5 are complex, rhPDCD5 may increase the cytotoxicity of anti-tumor drugs by promoting the caspase-3-related apoptosis, influencing cell cycle, decreasing the expression of drug-resistant genes and reversing drug-resistance.

关 键 词：PDCD5蛋白 化疗增敏 凋亡 细胞周期 耐药 

分 类 号：R979.1[医药卫生—药品] R733.7[医药卫生—药学]