bcl-2基因的反义寡核苷酸与三氧化二砷联合对恶性淋巴瘤细胞系凋亡的影响  

Combinational effects of bcl-2 antisense oligodexynucleotide with arsenic trioxide on malignant lymphoma cell lines

作　　者：聂林[1] 张洹[2] 张建军[3] 王随照[3] 

机构地区：[1]暨南大学医学院第一附属医院肿瘤科,广东广州510630 [2]暨南大学医学院血液病研究室,广东广州510630 [3]广东省人民医院检验科,广东广州510080

出　　处：《中国癌症杂志》2002年第3期197-200,共4页China Oncology

基　　金：广东省重点基金项目 (No:99M0 12 0 4G);广州市重点基金项目 (No :2 0 0 1 Z 0 3 7 0 1 1)

摘　　要：目的 :研究bcl 2基因的反义寡核苷酸与三氧化二砷 (As2 O3 )联合对恶性淋巴瘤细胞系凋亡的影响。方法 :采用细胞染色方法观察细胞凋亡的形态 ,原位末端标记法 (TUNEL)检测凋亡细胞 ,流式细胞仪检测细胞的DNA含量和bcl 2蛋白的表达。结果 :10～ 4 0 μmol/Lbcl 2基因的反义寡核苷酸和 0 .5～ 2 .0 μmol/L三氧化二砷均能抑制恶性B淋巴瘤细胞系Raji细胞生长 ,诱导细胞凋亡 ,流式细胞仪检测Raji细胞 ,发现亚G1期细胞明显增多 ,bcl 2蛋白的表达明显降低 ,呈现时间剂量依赖效应 ,两者联合应用比单独应用抑制作用显著。结论 :bcl 2基因的反义寡核苷酸与三氧化二砷联合应用 ,明显抑制恶性B淋巴瘤细胞系生长 。Purpose:To investigate the effects of bcl 2 antisense phosphorothioate oligodeoxynucleotides (ASODN) combined with arsenic trioxide on the malignant lymphoma cell lines.Methods:Apoptosis, cellular DNA contents and bcl 2 expression were determined by cell stain, TdT mediated dUTP Nick end Labeling (TUNEL) and flow cytometry. Results:10～40μmol/L bcl 2 ASODN and 0.5～2.0 μmol/L As 2 O 3 could inhibit Raji cell growth and induce apoptosis significantly. Number of Sub G 1 cells significantly increased and Bcl 2 protein expression in Raji cells significantly was downregulated by flow cytometry assay. The relationship between level of bcl 2 protein and concentrations of As 2 O 3 and bcl 2 ASODN showed a dose and time dependent effect; so did the number of Sub G 1 cells. There is much more effective inhibition of growth and induction of apoptosis by their combination than alone. Conclusions:It is found that bcl 2 ASODN could significantly inhibit the growth of B lymphoma cell lines and induce their apoptosis when combined with arsenic trioxide.

关 键 词：三氧化二砷 淋巴瘤 BCL-2基因 反义寡核苷酸 细胞凋亡 

分 类 号：R733.4[医药卫生—肿瘤]