摘要
目的 探讨As2 O3 诱导耐药急性早幼粒细胞白血病 (APL)细胞凋亡的机制。方法 以耐维甲酸早幼粒白血病细胞株MR2为研究对象 ,非耐药早幼粒细胞白血病NB4为对照组 ,利用流式细胞仪、DNA电泳、免疫组化等手段 ,观察As2 O3 治疗耐药APL细胞的效应途径。结果 As2 O3 能显著诱导MR2细胞凋亡。MR2细胞P 糖蛋白 (PgP)表达 (30 %～ 40 % )较NB4细胞 (10 %～ 2 0 % )明显增强 (P <0 0 0 1) ,MR2细胞topoⅡβ表达 (17 6± 6 18～ 2 6 5± 10 0 1)较NB4细胞 (2 8 8± 3 37～38 3± 9 2 8)明显降低 (P <0 0 5 )。 0 5～ 2 0 μmol/LAs2 O3 能显著降低MR2细胞PgP表达和增强topoⅡβ表达 (P均 <0 0 5 )。结论 topoⅡβ表达降低和PgP高表达可能参与维甲酸耐药机制。调节topoⅡβ和PgP表达可能是As2 O3
Objective To investigate the possible mechanisms of arsenic trioxide induced apoptosis of retinoic acid(RA) resistant to acute promyelocytic leukemia(APL).Methods APL cell line MR2 resistant to RA was used for in vitro studies.APL cell line NB4 was used for control.The effect of As 2O 3 on MR 2 cell line was observed by using flow cytometry,DNA electrophoresis,and immunocytochemical assays.Results As 2O 3 could induced apoptosis of MR2 cell.The P glycoprotein(PgP) expression rates were significantly higher in MR2 cell line(30%～40%)than in NB4 cell line(10%～20%)( P< 0 001).The expressions of DNA topoisomerase Ⅱβ(topoⅡβ)were significantly lower in MR2 cell line(17 6±6 18～26 5±10 01)than in NB4 cell line(28 8±3 37～38 3±9 28)( P< 0 05).0 5～2 0μmol/L As 2O 3 significantly decreased the PgP expression and increased topoⅡβ expression in MR2 cell line.( P< 0 05).Conclusions The lower expression of topoⅡβ and the higher expression of PgP might take part in the retinoic acid resistant leukemia mechanisms.Regulation of the expression of topoⅡβ and of PgP might be one of the mechanisms of As 2O 3 induced MR2 cell apoptosis.
出处
《江苏医药》
CAS
CSCD
2000年第10期769-771,共3页
Jiangsu Medical Journal
