磁性纳米Fe_3O_4颗粒对藤黄酸诱导的U937细胞凋亡效应的影响(英文)  

Effects of Magnetic Nanoparticle of Fe_3O_4 on Apoptosis Induced by Gambogic Acid in U937 Leukemia Cells

作　　者：梁艺琼[1] 陈宝安[1] 吴玮玮[1] 高峰[1] 夏国华[1] 邵泽叶[1] 程坚[1] 丁家华[1] 高冲[1] 李国宏[1] 陈文姬[1] 陈宁娜[1] 许文林[2] 孙新臣[3] 刘莉洁[4] 李小毛 王雪梅[6] 

机构地区：[1]东南大学临床医学院附属中大医院血液科,江苏南京210009 [2]江苏大学人民医院血液科,江苏镇江212002 [3]东南大学中大医院肿瘤科,江苏南京210009 [4]东南大学生理教研室,江苏南京210009 [5]萨尔大学物理系,德国萨尔布吕肯d66041 [6]东南大学生物电子学国家重点实验室,江苏南京210096

出　　处：《中国实验血液学杂志》2010年第1期67-73,共7页Journal of Experimental Hematology

基　　金：supported by National 863 Program Emphasis Project(Nanometer Biology Ware Study,No.2007AA0222007);National Nature Science Foundation of P.R.China(No.30740062 and No.30872970);High School DoctorSubject Special-purpose Scientific Research Foundation(No.20070286042)

摘　　要：本研究探讨联合应用藤黄酸(GA)和磁性纳米Fe3O4颗粒(MNP-Fe3O4)治疗白血病的潜在可能性。采用MTT法检测GA对U937的细胞毒作用及GA联合MNP-Fe3O4对U937细胞生长抑制的影响;流式细胞术检测细胞凋亡率;应用Wright及DAPI染色观察凋亡细胞的形态学变化;采用实时定量RT-PCR及Western blot法分别检测细胞的caspase-3、bcl-2、bax、NF-κB和survivin基因及相应蛋白的表达。结果表明:GA对U937细胞的生长抑制作用呈现时间及剂量依赖性;MNP-Fe3O4本身无细胞毒作用,但能使GA对U937细胞的生长抑制作用增强;联合应用GA和MNP-Fe3O4诱导的细胞凋亡率较单用GA明显增加,细胞呈现典型的凋亡形态改变,同时可见caspase-3及bax表达上调,而凋亡抑制基因如bcl-2、NF-κB和survivin表达下调。结论:MNP-Fe3O4能增强GA对U937细胞的凋亡诱导作用,两者联合应用可能是一种新型而安全有效的白血病治疗方法。This study was aimed to explore the potential therapy of Gambogic acid（GA） combinated with magnetic nanoparticle of Fe3O4 （Fe3 O4-MNP） on leukemia. The proliferation of U937 cells and the cytotoxcity were evaluated by MTT assay, Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe304-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3 04-MNP was higher than that by GA alone. The typical aptop- totic features of cells treated with GA and Fe3 04-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-KB and survivin were down-regulated. It is concluded that Fe3 O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.

关 键 词：藤黄酸 磁性纳米Fe3O4颗粒 细胞凋亡 U937细胞 

分 类 号：R979.1[医药卫生—药品] R733.7[医药卫生—药学]