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目的 了解三氧化二砷 (As2 O3 )联合 8 对氯苯硫基环腺苷酸 (8 CPT cAMP)对维甲酸(RA)耐药的急性早幼粒细胞白血病 (APL)细胞的作用。方法 以RA耐药的APL细胞株NB4 R1和NB4 R2为模型 ,通过观察细胞生长、形态、表面分化抗原以及对四氮唑蓝的还原能力的改变来研究As2 O3 、8 CPT cAMP单独和联合对细胞增殖及分化的影响 ;并应用免疫荧光和Westernblot检测药物处理前后细胞内PML RARα融合蛋白以及细胞周期调控蛋白的变化。结果 低剂量As2 O3 (0 .2 5 μmol L)与 8 CPT cAMP(2 0 0 μmol L)可协同促进NB4 R1和NB4 R2细胞分化。 8 CPT cAMP可通过影响细胞周期调控蛋白E2F和P2 1的表达而抑制细胞增殖 ,并促进As2 O3 介导的PML RARα融合蛋白降解。结论 As2 O3 联合 8 CPT cAMP能够诱导RA耐药的APL细胞分化。
Objective To investigate the effect of arsenic trioxide (As 2 O 3) combined with 8-CPT cAMP on RA-resistant acute promyelocytic leukemia (APL) cells. Methods The models of As3O3, 8 CPT cAMP alone and in combination were studied by observing cell growth, morphology, surface differentiation antigen and reducing ability of tetrazolium blue in RA resistant APL cell line NB4 R1 and NB4 R2 Cell proliferation and differentiation. The changes of intracellular PML RARα fusion protein and cell cycle regulatory protein before and after drug treatment were detected by immunofluorescence and Western blot. Results Low doses of As 2 O 3 (0.25 μmol L) and 8 CPT cAMP (200 μmol L) promoted the differentiation of NB4 R1 and NB4 R2 cells. 8 CPT cAMP can inhibit cell proliferation by affecting the expression of cell cycle regulatory proteins E2F and P2 1 and promote As 2 O 3 -mediated degradation of PML RARα fusion protein. Conclusion As2 O3 combined with 8 CPT cAMP can induce RA-resistant APL cell differentiation.