摘要
目的探讨三氧化二砷(As_2O_3)磁性四氧化三铁(Fe_3O_4)白蛋白微球对人卵巢癌细胞耐药性的作用及其可能机制。方法体外培养人卵巢癌顺铂耐药细胞株SKOV3/CDDP,随机分为阴性对照组(A组)、交变磁场(AMF)组(B组)、Fe_3O_4白蛋白微球组(C组)、Fe_3O_4白蛋白微球联合AMF组(D组)、As_2O_3白蛋白微球组(E组)、As_2O_3磁性Fe_3O_4白蛋白微球联合AMF组(F组)和顺铂溶液组(G组)。采用MTT法和流式细胞术分别检测细胞生长和凋亡情况,RT-PCR法检测凋亡相关基因Bcl-2、Bax和Caspase-3mRNA表达,Western blot法检测多重耐药蛋白1(MDR1)、多重耐药相关蛋白2(MRP2)的蛋白表达。结果A、B、C组间细胞生长和凋亡情况无统计学差异(P>0.05)。与A组和G组相比,D、E、F组细胞生长抑制率和凋亡率增加,Bax和Caspase-3mRNA表达升高,Bcl-2mRNA以及MDR1、MRP2蛋白表达降低(P<0.05),F组各指标变化更为明显(P<0.05)。结论 As_2O_3磁性Fe_3O_4白蛋白微球联合AMF能有效逆转SKOV3/CDDP细胞耐药性;其作用机制可能与下调Bcl-2、MDR1、MRP2以及上调Bax、Caspase-3的表达有关。
Objective To investigate the effect and underlying mechanism of arsenic trioxide （As2 O3 ）-loaded magnetic ferroferric oxide （Fe3 O4 ）albumin nanospheres on multidrug resistance of human ovarian cancer cells .Methods SKOV3/CDDP cells were cultured in vitro and divided into sevengroups of A（negative control）,B[treated with alternating magnetic field（AMF）],C（treated with Fe3O4 albumin nanospheres） ,D（treated with Fe3O4 albumin nanospheres combined with AMF） , E（treated with As2O3 albumin nanospheres） ,F（treated with As2O3-loaded magnetic Fe3O4 albumin nanospheres combined with AMF） and G（treated with cisplatin） .The cell growth and apoptosis were determined by MTT and flow cytometry ,respectively .The mRNA expressions of Bcl-2 ,Bax and Caspase-3 were measured by RT-PCR .The protein expressions of multidrug resistance drug protein 1 （MDR1） and multidrug relative proteins 2（MRP2） were detected by Western blot .Results There was no statistical difference in cell growth and apoptosis among groups of A ,B and C （P〉0 .05） . Compared with groups of A and G ,the rates of growth inhibition and apoptosis were increased ,mRNA expressions of Bax and Caspase-3 were up-regulated ,and expressions of Bcl-2 mRNA ,MDR1 protein and MRP2 protein were down-regulated in groups of D ,E and F（P〈0 .05） ,which were changed more obviously in group F （ P〈0 .05 ） .Conclusion As2 O3-loaded magnetic Fe3 O4 albumin nanospheres combined with AMF can effectively reverse multidrug resistance of SKOV 3/CDDP cells ,which may be associated with down-regulation of Bcl-2 ,MDR1 and MRP2 expressions and up-regulation of Bax and Caspase-3 expressions .
出处
《江苏医药》
CAS
2016年第19期2077-2081,共5页
Jiangsu Medical Journal
基金
南京医科大学科技发展基金重点项目(2012NJMU094)
关键词
热化疗
三氧化二砷
多重耐药性
凋亡
Thermochemotherapy
Arsenic trioxide
Multidrug resistance
Apoptosis
