丙戊酸钠协同阿霉素抑制骨髓增生异常综合征细胞株增殖并诱导其凋亡  

Sodium Valproate Synergizes Adriamycin to Inhibit Proliferation and Induce Apoptosis in Myelodysplastic Syndrome Cell Line

作　　者：俞晨[1] 陈宝安[1] 高冲[1] 丁家华[1] 夏国华[2] 邵泽叶[2] 高峰[2] 孙耘玉[1] 程坚[1] 赵刚[1] 王骏[1] 宋慧慧[1] 马燕[1] 鲍文[1] 

机构地区：[1]东南大学附属中大医院血液科,江苏南京210009 [2]东南大学临床医学院中心实验室,江苏南京210009

出　　处：《中国实验血液学杂志》2008年第3期555-560,共6页Journal of Experimental Hematology

基　　金：国家自然基金资助项目,编号30070318

摘　　要：本研究探讨丙戊酸钠(SVPA)协同阿霉素(ADM)抑制骨髓增生异常综合征细胞株MUTZ-1增殖并诱导其凋亡的作用。采用细胞形态学方法观察小剂量SVPA和ADM处理后细胞形态的改变,应用(MTT)比色法检测SVPA及ADM对细胞生长的抑制作用,流式细胞术分析细胞凋亡。结果表明:不同浓度的ADM(0.039μg/ml、0·078μg/ml、0.156μg/ml、0.312μg/ml和0.4μg/ml)与0.25mmol/LSVPA联合作用于MUTZ-1细胞72小时后,细胞抑制率分别为(23.46±1.12)%、(49.87±0.84)%、(52.37±1.05)%、(78.43±4.34)%和(82.47±1·04)%,明显高于单用ADM时的(5.08±0.79)%、(12.32±2.39)%、(23.65±1.34)%、(43.33±2.38)%和(47.85±1·46)%(p<0.05)。单用0.25mmol/LSVPA时对细胞生长无影响(p>0.05)。SVPA联合ADM作用细胞株72小时后,细胞呈现典型的凋亡细胞的形态学特征;SVPA和ADM联合作用后细胞的凋亡率比单独使用ADM明显增加,并呈浓度依赖性,与对照组相比有显著的统计学意义,其中以0.078μg/ml浓度ADM为最佳抑制浓度。结论:小剂量的SVPA能增敏ADM诱导骨髓增生异常综合征细胞株MUTZ-1发生凋亡。The aim of this study was to investigate the tumor suppression efficacy of a histone deacetylase inhibitor, sodium valproate combined with adriamycin in the treatment of myelodysplastic syndrome cell line MUTZ-1. After treated with different concentrations of sodium valproate alone, adriamycin alone or combination of them, growth curve of MUTZ-1 cell line were detected; growth of the tumor cells were analyzed by flow cytometry and morphology method. The results indicated that when the myelodysplastic syndrome cell line MUTZ-1 was treated with adriamycin （0.039 μg/ ml, 0.078 μg/ml, 0. 156 μg/ml, 0.312 μg/ml, 0.4 μg/ml）, the tumor growth inhibition rates were 5.08 ± 0.79%, 12.32 ± 2.39%, 23.65 ± 1.34%, 43.33 ± 2.38% and 47.85 ± 1.46% （p 〈 0.05 ）, 0.25 mmol/L sodium valproate did not show apoptosis effect, but could synergize adriamycin to promote apoptosis. When the myelodysplastic syndrome cell line MUTZ-1 treated with two drug combination, the tumor growth inhibition rates were 23.46 ± 1.12%, 49.87 ± 0.84%, 52.37 ± 1.05%, 78.43 ± 4.34% and 82.47 ± 1.04% （p 〈 0.05 ） , and displayed concentration-dependent manner. All the data above were significantly different from those in control （p 〈0.05） . Sodium valproate showed obvious effect at concentration of 0.078 μg/ml adriamycin. After treated with 0.25 mmol/L sodium valproate and 0.078 μg/ml adriamycin for 72 hours, MUTZ-1 cell line showed typical apoptosis morphological character. It is concluded that sodium valproate may enhance the efficacy of adriamycin on MUTZ-1 cell line.

关 键 词：丙戊酸钠 阿霉素 骨髓增生异常综合征 MUTZ-1细胞株 细胞凋亡 

分 类 号：R733.3[医药卫生—肿瘤] R979.1[医药卫生—临床医学]