NF-κB和存活蛋白抑制药物诱导的倍体化与衰老巨核细胞的死亡  

Survivin and NF-κB(p65) Inhibit the Death of Senescent and Polyploidy Megakaryocyte Induced by Drugs

作　　者：杨金刚[1] 周丽[1] 郭通[1] 刘硕[1] 周凡[2] 马东初[1] 

机构地区：[1]沈阳军区总医院医学实验科,辽宁沈阳110016 [2]沈阳军区总医院血液科,辽宁沈阳110016

出　　处：《生物技术通讯》2016年第4期492-496,共5页Letters in Biotechnology

基　　金：国家自然科学基金(31571398);辽宁省自然科学基金(2015020434)

摘　　要：目的:筛选诱导巨核细胞倍体化药物,研究倍体化细胞的抗死亡机制,探索促进倍体化细胞死亡的用药方法。方法:采用不同药物处理巨核细胞白血病细胞系Dami细胞,检测细胞倍性、衰老、死亡及相关分子的变化。结果:Nocodazole、SP600125与SU6668可阻断Dami细胞增殖,诱导倍体化,促进细胞衰老,短期诱导不影响细胞活力。分子水平表明,抗凋亡分子存活蛋白表达上调,衰老相关分泌表型调控因子NF-κB(p65)活性降低。持续的药物诱导可致细胞死亡。结论:诱导巨核细胞倍体化抑制恶性增殖,促进细胞衰老发生,存活蛋白与NF-κB(p65)共同抑制倍体化和衰老细胞的死亡,而持续的药物诱导可促进细胞死亡,可作为急性巨核细胞白血病的治疗策略。Objective： To screen the drug induced megakaryocyte polyploidization, study the anti-apoptosis mech-anism of polyploid cells, and explore the medication method promoting death of polyploid cells. Methods： Usingdifferent drugs to treated Dami cells, and detecting the change of cells ploidy, the situation of senescence anddeath, and the changes of related molecules. Results： Nocodazole, SP600125 and SU6668 blocked proliferation, in-duced polyploidization and senescence, but did not affect the cells vitality. Molecular level shown that expressionof survivin, an anti-apoptosis molecule, was increased; the activity of NF-κB（p65）, a regulation factor of senes-cence-associated secretory phenotype, was reduced. Continuous induction can cause cells death. Conclusion： Mega-karyocyte polyploidizations induced by drugs inhibit malignant proliferation, and promote cell senescence. Survivinand NF-κB（p65） inhibit the death of senescent and polyploidy cells, and consistent induction by drug can pro-mote cells death. Our research can be used as AMKL treatment strategy.

关 键 词：巨核细胞 倍体化 衰老 存活蛋白 NF-ΚB 凋亡 

分 类 号：Q25[生物学—细胞生物学]