携带pdcd5基因的增殖型腺病毒与VP-16杀伤K562细胞的协同作用  

Synergistic Killing Effect of the Conditionally Replicating Adenoviruses Carrying Programmed Cell Death 5 Gene and Etoposide on K562 Cells

作　　者：谢敏[1] 常艳[1] 牛继红[1] 张瑶[1] 李金兰[1] 吴红平[2] 李琳芳[2] 黄晓军[1] 阮国瑞[1] 

机构地区：[1]北京大学人民医院,北京大学血液病研究所,北京100044 [2]第二军医大学东方肝胆外科医院病毒和基因治疗中心,上海200438

出　　处：《中国实验血液学杂志》2010年第6期1435-1439,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金,编号30670894

摘　　要：程序性细胞死亡因子5(programmed celldeath5,PDCD5)在多种肿瘤细胞中表达明显降低。携带pdcd5基因的靶向增殖型腺病毒SG611-pdcd5对白血病细胞具有杀伤作用,对正常细胞具有相对保护作用。本研究旨在观察联合应用SG611-pdcd5与低剂量化疗药物依托泊甙(etoposide,VP-16)对白血病细胞系K562的作用。以不同浓度梯度的药物或不同感染复数(multiplicity of infection,MOI)的病毒液作用于K562细胞,培养48小时后用MTT法检测细胞存活率。结果表明,与SG611-pdcd5(MOI=40)或VP-16(0.5μg/ml)单独作用组相比,SG611-pdcd5(MOI=40)+VP-16(0.5μg/ml)组细胞存活率明显降低(p均<0.05),分别为(59.45±4.12)%、(82.91±3.41)%及(42.00±5.75)%。SG611-pdcd5与VP-16的协同作用强于PDCD5蛋白或携带pdcd5基因的非增殖型腺病毒Ad-pdcd5与VP-16的协同作用(p均<0.05);VP-16浓度为4.0μg/ml时,VP-16+SG611-pdcd5(MOI=40)组、VP-16+proPDCD5(40μg/ml)组及VP-16+Ad-pdcd5(MOI=80)组细胞存活率分别为(37.09±1.89)%、(52.36±1.64)%及(73.64±4.33)%。结论:SG611-pdcd5具有促进低剂量VP-16杀伤K562细胞的作用,二者联合可增强对白血病细胞的杀伤作用。The expression levels of programmed cell death 5 （PDCD5） are down-regulated in many malignancies. SG611-pdcd5,a recombinant conditionally replicative adenovirus carrying pdcd5 gene expression cassette,can evidently kill the leukemic cells and protect selectively the normal cells. The purpose of this study was to investigate the synergistic killing effect of SG611-pdcd5 and low-dose etoposide （VP-16） on K562 cells. K562 cells were treated with different concentrations of VP-16 or different multiplicities of infection （MOI） of SG611-pdcd5. After 48 hours of incubation the cell viability was determined by using MTT assay. The results showed that the cell viability of SG611-pdcd5 （MOI=40） plus VP-16（0.5 μg/ml） group significantly decreased as compared with single SG611-pdcd5 （MOI=40） treatment group or single VP-16（0.5 μg/ml） treatment group （42.00±5.75% vs 59.45±4.12%; 42.00±5.75% vs 82.91±3.41%,respectively,both p0.05）. The synergistic killing effect of SG611-pdcd5 plus VP-16 was higher than that of PDCD5 protein plus VP-16 or that of non-replicating adenovirus carrying pdcd5 （Ad-pdcd5） plus VP-16 （both p0.05）. The cell viability of VP-16 （4.0 μg/ml） plus SG611-pdcd5 （MOI=40） group,VP-16 （4.0 μg/ml） plus proPDCD5（40 μg/ml） group and VP-16 （4.0 μg/ml） plus Ad-pdcd5（MOI=80） group was 37.09±1.89%,52.36±1.64% and 73.64±4.33%,respectively. It is concluded that SG611-pdcd5 can promote K562 cell death induced by low-dose VP-16. The combination of SG611-pdcd5 and VP-16 can enhance the killing effect on leukemic cells.

关 键 词：pdcd5基因 VP-16 增殖型腺病毒 K562细胞 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]