三氧化二砷联合丁硫氨酸亚砜胺诱导人白血病K562／ADM细胞凋亡  

Arsenic trioxide combined with buthionine sulfoximine enhances apoptosis in multidrug.resistant human leukemia K562/ADM cells in vitro

作　　者：王涛[1] 马梁明[1] 张华屏[2] 王宏伟[1] 杨林花[1] 乔振华[1] 

机构地区：[1]山西医科大学第二医院血液科,030001 [2]山西医科大学实验中心

出　　处：《中华肿瘤杂志》2008年第3期188-191,共4页Chinese Journal of Oncology

摘　　要：目的观察三氧化二砷（As2O3）联合丁硫氨酸亚砜胺（BSO）对肿瘤多药耐药细胞K562／ADM的诱导凋亡效应，探讨谷胱甘肽（GSH）的含量变化对As2O3作用效果的影响。方法以0．5、2．0、5．0μmol／L As2O3单独及联合100μmol／LBSO作用于K562／ADM细胞，应用二苯基溴化四氮唑蓝（MTT）比色法检测细胞的增殖活性，Annexin V／PI标记法观察细胞的凋亡效应，分光光度法检测细胞内GSH含量的变化。结果K562／ADM细胞内GSH含量为（81．13±3．91）mg／g prot，明显高于K562细胞（P〈0．01）。BSO单独或联合As2O3作用下，随作用时间的延长，K562／ADM细胞内GSH含量逐渐降低。临床剂量（0．5、2．0μmol／L）As2O3联合BSO作用下，抑制作用逐步增强，72h两组的细胞增殖抑制率分别为（90．63±5．95）％和（86．12±6．11）％，均分别高于单用相应剂量As203组（P〈0．01）；凋亡效应逐步增强，72h两组的细胞凋亡率分别为（82．15±9．28）％和（92．72±9．41）％，均分别高于单用相应剂量灿203组（P〈0．01）。结论GSH的含量变化与As2O3的作用效果密切相关，As2O3联合BSO可有效诱导K562／ADM细胞发生凋亡。Objective To investigate the apoptosis-inhancing effect of the combination of arsenic trioxide （As2O3 ） and buthionine sulfoximine （BSO） on multidrug-resistant human leukemic K562/ADM ceils, to compare the effect of As2O3 alone and As2O3 combined with BSO and As2O3 alone, and to determine the effect of intraceilular GSH content on this treatment. Methods As2O3 was used in a dose of 0.5 μmol/L,2.0 μmol/L and 5.0 μmol/L, respectively, and BSO was used in a dose of 100 μmol/L in the culture of multidrug-resistant human leukenic K562/ADM ceils. The ceil proliferation activity was assessed with MTT assay. The ceil apeptosis was detected by flow cytometry using Annexin-V and propidium iodide （PI） staining. Intraceilular GSH content was measured using glutathione assay kit by spectrophotometry. Results After the GSH contents were reduced by the combination of arsenic in clinic dose （0.5,2 μmol/L） and BSO （100 μmol/L）, respectively, the K562/ADM cell proliferation activity was obviously inhibited and the cell apeptosis-inducing effect was advanced in 24 hours. In 48 and 72 hours, the effect of the combination group （clinic dose arsenic group ） was significantly stronger than that of clinic dose arsenic alone group and the high dose arsenic alone group. Conclusion The cell apeptosis-inducing effect of arsenic in combination of BSO on multidrug resistant human leukemia K562/ADM cells is significantly enhanced in comparison with that of arsenic alone. The reduction of intraceilular glutathione content is closely correlated with this apeptosis-enhancing effect.

关 键 词：多药耐药 三氧化二砷 谷胱甘肽 凋亡 

分 类 号：R686[医药卫生—骨科学]