STI571、三氧化二砷和Velcade对bcr/abl^+-CD34^+细胞增殖、凋亡的影响  

STI571 enhances the effect of arsenic trioxide and Velcade on bcr/abl^+-CD34^+ cell proliferation and apoptosis

作　　者：李澄宇[1] 孟凡义[1] 孙启鑫[1] 扶云碧[1] 李利[1] 易正山[1] 宋兰林[1] 

机构地区：[1]南方医科大学南方医院血液科,广东广州510515

出　　处：《南方医科大学学报》2007年第11期1665-1669,共5页Journal of Southern Medical University

基　　金：广东省科技计划攻关项目(B30202)~~

摘　　要：目的研究STI571、三氧化二砷(As2O3)和Velcade在单独及联合应用时对bcr/abl+-CD34+细胞增殖、凋亡的影响。方法提取慢性粒细胞白血病患者骨髓的bcr/abl+-CD34+细胞,用STI571、As2O3、Velcade单独及联合处理96h,通过CCK-8分析及流式细胞术分别检测细胞增殖、凋亡的变化,并用Hoechst33342染色及荧光显微镜技术观察凋亡细胞形态学改变。同时检测上述方案对正常骨髓CD34+细胞的抑制作用。结果STI571、As2O3及Velcade对bcr/abl+-CD34+细胞的作用呈剂量依赖性,其中在低浓度时以抑制增殖作用为主,促凋亡作用不明显。当0.25～2μmol/LSTI571分别与2.5μmol/LAs2O3及15nmol/LVelcade联合后,抑制率和凋亡率均显著提高,呈相加或协同作用,且对正常CD34+细胞的抑制作用无进一步增强。结论As2O3及Velcade与STI571联合能够增强对BCR/ABL+-CD34+细胞的作用,具有一定临床意义。Objective To study the effects of STI571, arsenic trioxide （As2O3） and Velcade, used alone or in combination, on the proliferation and apoptosis of bcr/abl^＋-CD34^＋ cells. Methods bcr/abl^＋-CD34^＋ cells isolated from the bone marrow of patients with chronic myeloid leukemia （CML） were treated for 96 h with STI571, As2O3 and Velcade either alone and in combination, and the cell proliferation and apoptosis were analyzed by CCK-8 assay and flow cytometry. The morphological changes of the apoptotic cells were observed by Hoechst33342 staining and fluorescent microscope. The inhibitory effects of the drugs on normal CD34^＋ cells were also observed. Results Low-concentration STI571, As2O3 or Velcade all dose-dependently inhibited bcr/abl^＋-CD34^＋ cell proliferation without obvious apoptosis-inducing effects. STI571 at 0.25-2μmol/L combined with As2O3 at 2.5 μno]/L and with Velcade at 15 nmol/L both significantly increased the cell inhibition and apoptosis rates, showing obvious additive or synergistic effects of the drugs without further enhancement of normal CD34^＋ cell inhibition. Conclusion Combination with STI571 enhances the effects of As2O3 and Velcade on bcr/abl^＋-CD34^＋ cells, suggesting the potential clinical value of this regimen.

关 键 词：BCR/ABL CD34^+细胞 STI571 三氧化二砷 VELCADE 

分 类 号：R733.7[医药卫生—肿瘤]