PML—RARα表达对细胞凋亡诱导剂敏感性差异的分子机制研究  

Molecular mechanism of different sensitivities of PML-RARα to apoptosis induced by apoptosis inducing agents

作　　者：赵海涛[1] 温培娥[1] 任霞[1] 杨炜华[1] 范华[1] 乔高娟[1] 唐天华[1] 任海全[1] 毕可红[2] 姜国胜[1] 

机构地区：[1]山东省医学科学院基础医学研究所,山东省医药卫生肿瘤免疫与中药免疫重点实验室,济南250062 [2]山东大学附属千佛山医院

出　　处：《国际肿瘤学杂志》2009年第5期394-397,共4页Journal of International Oncology

基　　金：国家自然科学基金资助项目（30771103）;山东省自然科学基金资助项目（2008GG2NS02023）;山东省科技攻关课题（Y2008C165）

摘　　要：目的研究PML—RARα表达阴性的HL-60细胞和表达阳性的NB4细胞对三氧化二砷（As2O3）诱导细胞凋亡敏感性差异的分子机制。方法经As2O3作用人急性早幼粒细胞白血病HL-60和NB4细胞后，MTT法检测细胞增殖变化，流式细胞术测定细胞凋亡水平的变化，RT—PCR检测Bcl-2、Bax、Fas等基因在mRNA水平的表达变化。结果As2O3可诱导NB4细胞出现明显的凋亡现象，细胞增殖受到明显抑制（P〈0．05），Bcl-2基因表达明显下调（P〈0．05），但Bax、Fas基因表达没有明显变化（P〉0．05），Bcl-2／Bax比值明显降低（P〈0．05）。而对于PML—RARα表达阴性的HL-60细胞，经小剂量As2O3作用后，对细胞的增殖抑制作用不明显（P〉0．05），未出现明显凋亡现象，Bcl-2、Bax、Fas或Bcl-2／Bax表达水平及比值变化不明显（P〉0．05）。结论Bcl-2／Bax表达比值变化与否，可能是小剂量As2O3诱导PML—RARα表达阴性的HL-60细胞和表达阳性的NB4细胞发生凋亡差异的分子机制。Objective To study the molecular mechanism of different sensitivities to apoptosis induced by low concentration of As203 in PML-RARα negative HL-60 cells and PML-RARα positive NB4 cells. Methods NB4 and HL-60 cells were cultured with As203 for 1 to 4 days; cell proliferation were detected by MTT method; the apoptosis was detected by flow cytometry,Bcl-2,Bax and Fas mRNA were determined by RT-PCR. Results The proliferation of NB4 cells was inhibited obviously by As2O3 （ 1.0 μmol/L） with the induction of apoptosis（ P 〈 0. 05 ）, which was accompanied by the down-regulation of Bel-2 mRNA expression（ P 〈 0. 05 ） and the ratio of Bcl-2/Bax （P 〈 0. 05 ）, but there was no obvious variation of Bax and Fas expression（ P 〉 0. 05 ）. Inhibition of proliferation and apoptosis were not obvious in PML-RARα negative HL-60 cells induced by low concentration As2O3 （ P 〉0. 05）, and there was no obvious variation of Bcl-2, Bax, Fas mRNA expression or Bcl/Bax ratio（ P 〉 0. 05 ）. Conclusion The ratio of Bcl-2/Bax is contributed to the different sensitivities of PML-RARα negative HL-60 cells and positive NB4 cells induced by low concentration of As2O3.

关 键 词：细胞凋亡 砷剂 诱导剂 敏感性差异 PML-RARΑ 肿瘤 

分 类 号：R73-3[医药卫生—肿瘤]