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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 诱导MR2细胞凋亡的机制之一
Objective To investigate the mechanism of apoptosis induced by As2 O3 in acute promyelocytic leukemia (APL) cells. Methods The MR2 cell line resistant to retinoic acid was used as the research object, and the non-drug resistant promyelocytic leukemia NB4 was used as the control group. Flow cytometry, DNA electrophoresis and immunohistochemistry were used to observe the resistance of As2 O3 APL cell effector pathways. Results As2 O3 significantly induced apoptosis in MR2 cells. Compared with NB4 cells (10% ~ 20%), the expression of Pgp in MR2 cells was significantly increased (P <0.01), while the expression of topoⅡβ in MR2 cells was significantly (17 6 ± 6 18 ~ 2 6 5 ± 10 0 1) was significantly lower than that of NB4 cells (2 8 8 ± 3 37 ~ 38 3 ± 9 2 8) (P 0 05). 0 2-20 μmol / L As 2 O 3 could significantly decrease the expression of PgP and enhance the expression of topoⅡβ in MR2 cells (all P <0.05). Conclusion The decrease of topoⅡβ expression and the high expression of PgP may be involved in the mechanism of retinoic acid resistance. Regulation of topoⅡβ and PgP expression may be one of the mechanisms of As2 O3-induced apoptosis in MR2 cells