CpG ODN对急性单核细胞白血病细胞株U937化疗敏感性的影响及其机制研究  

Effect of CpG ODN on chemosensitivity of acute monocytic leukemia cell line U937 and its mechanism

作　　者：王瑾[1] 宋珂珂 马肖容[1] 张王刚[1] 何爱丽[1] WANG Jin;SONG Keke;MA Xiaorong;ZHANG Wanggang;HE Aili(Department of Hematology,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]西安交通大学第二附属医院血液内科

出　　处：《西部医学》2019年第12期1814-1819,1825,共7页Medical Journal of West China

基　　金：国家自然科学基金青年项目(81100374);陕西省重点研发计划一般项目(2018SF-004);中央高校基本科研业务费专项资金(xjj2018135)

摘　　要：目的观察CpG ODN对人急性单核细胞白血病细胞株U937化疗敏感性的影响,探讨增强急性白血病化疗效果的可能途径及其作用机制。方法多柔比星(ADM)单药及联合应用CpG ODN与U937细胞共同孵育,采用CCK-8法检测U937细胞生长抑制率,Hoechst染色法和流式细胞仪Annexin V-PI双染法检测U937细胞的凋亡情况,RT-PCR检测分析凋亡相关基因Bcl-2和Bax的水平。结果ADM对U937细胞生长具有明显抑制作用,而且CpG ODN与其联合应用可进一步加强该作用。各浓度ADM+CpG ODN联合组对U937细胞的生长抑制率和诱导的早期凋亡率均显著高于ADM单药组(均P<0.05)。ADM+CpG ODN联合组细胞内Bax基因的mRNA表达量较ADM单药组明显上升(P<0.05),而Bcl-2 mRNA的表达无显著性差异(P>0.05)。ADM+CpG ODN联合组较ADM单药组的Bcl-2/Bax值减小(P<0.05)。结论CpG ODN可增强ADM对U937细胞生长的抑制作用,加强ADM诱导白血病细胞凋亡的作用,从而增强U937对ADM的化疗敏感性。该作用可能是通过上调Bax基因的表达而实现。Objective To observe the effect of CpG ODN on the chemosensitivity of human acute monocytic leukemia cell line U937 to doxorubicin(ADM)and explore the possible ways to enhance the chemosensitivity of acute leukemia and the mechanism.Methods Doxorubicin was used alone and combined with CpG ODN to incubate U937 cells.The growth inhibition rate of U937 cells was detected by CCK-8.Hoechst staining and Annexin V-PI double staining were used to detect the apoptosis of U937 cells.The levels of apoptosis-related genes Bcl-2 and Bax were detected by RT-PCR.Results ADM could inhibit the growth of U937 cells,and CpG ODN combined with ADM could further enhance the effect.The growth inhibition rate and early apoptotic rate of U937 cells in ADM+CpG ODN combination group were higher than those in ADM alone group(P<0.05).The expression of Bax gene in ADM+CpG ODN group was significantly higher than that in ADM group(P<0.05),but there was no significant difference in the expression of Bcl-2 gene between ADM+CpG ODN group and ADM group(P>0.05).Therefore,the Bcl-2/Bax value of ADM+CpG ODN combined group was lower than that of ADM single drug group(P<0.05).Conclusion CpG ODN can enhance the inhibitory effect of ADM on the growth of U937 cells and the apoptotic effect of ADM on leukemia cells,thus enhancing the chemosensitivity of U937 to ADM.This effect may be achieved by up-regulating the expression of Bax gene.

关 键 词：CpG ODN 急性白血病 U937 多柔比星 化疗敏感性 细胞凋亡 

分 类 号：R552[医药卫生—血液循环系统疾病]