抗CXCR4单克隆抗体12G5对阿糖胞苷杀伤HL-60细胞效应的影响  

Influence of Anti-CXCR4 Monoclonal Antibody 12G5 on Killing Effect of Cytosine Arabinoside to HL-60 Cell

作　　者：魏立[1] 孔佩艳[1] 陈幸华[1] 彭贤贵[1] 曾东风[1] 常城[1] 杨文博[1] 刘红[1] 刘林[1] 王庆余[1] 张怡[1] 

机构地区：[1]第三军医大学新桥医院血液科,重庆400037

出　　处：《中国实验血液学杂志》2005年第2期269-273,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金项目资助项目(编号30170396)

摘　　要：本研究通过观察抗CXCR4单克隆抗体12G5对Ara C杀伤HL-60细胞效应的影响,评价其在白血病骨髓 残留病变中的治疗价值。培养并共培养HL-60细胞,在共培养体系中采用12G5(10μg／ml)阻抑基质细胞SDF-1的 生物作用后,通过MTT法及细胞形态学观察检测不同浓度Ara c对HL-60细胞杀伤作用的变化。药物杀伤效应曲 线显示,在20μg／ml Ara C组,对照组中前2天A540值明显下降,但从3-4天开始出现上升,而加12G5实验组中 A540值虽然下降平缓,但持续下降,并于观察第5天后低于对照组,整个观察期中未出现反弹。在40μg／ml Ara C 组,对照组A540在0-3天明显下降,从第4天开始回升,于第5-6天与实验组曲线交叉,从7-12天时照组A540值 总体呈上升趋势,并明显高于实验组,而加12G5实验组曲线在整个观察期间虽然在7-9天有小幅度攀升,但总的 趋势是下降。细胞形态学观察显示,在两个浓度组,对照组HL-60细胞数量最初明显减少,随着培养时间延长,细 胞数量逐渐增多,实验组结果正相反。结论:12G5减弱Ara C对HL-60细胞的早期杀伤作用,但12G5增强Ara C 总体杀伤作用,同时,延缓HL-60细胞对Ara c的耐药性,因此12G5有助于白血病骨髓残留病变的治疗。This study was aimed to explore the influence of anti-CXCR4 monoclonal antibody 12G5 on killing effect of cytosine arabinoside (Ara C) to HL-60 cell, and to assess its therapeutic value in marrow residual disease. HL-60 cells were cultured and co-cultured with leukemic stromal cells, and SDF-1 activity was inhibited with 10 μg/ml 12G5, then, killing effects of Ara C on HL-60 cells were investigated by MTT and morphology assay. Curves by MTT assay revealed that in the test group of 20 μg/ml Ara C, A540 values decreased slowly but straightly, however, in control group A540 values decreased markedly for the first two days, and increased from day 3 or 4. In the test group of 40 μg/ml Ara C, although increasing at constricted range of 7 -9 days, A540 values decreased in whole observing period of 12 days, while in control group A540 values decreased markedly at day 0 - 3, and increased from day 4. Furthermore, two curves go across each other at day 5, and continue the increasing tendency. Morphology results showed that in both treated groups, the number of HL-60 cell decreased remarkedly and increased gradually in control group, but just contrary to test group. It is concluded that 12G5 may weaken the killing effect of Ara C on HL-60 cell in earlier period, but reinforce the total killing effect and delay the occurrence of drug resistence simultaneously. Thus 12G5 has the therapeutic potential on marrow residual disease.

关 键 词：CXCR4 12G5 单克隆抗体 阿糖胞苷 HL-60 残留白血病 药物敏感性 

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