环孢菌素A阻断人HL-60抗药性细胞于G1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的HL-60细胞(HR20)抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明,环孢菌素A(CsA)20,10μg·ml^-1诱导HL-60细胞发生凋亡,而阻断HR20细胞于G₁期,就不能诱导细胞发生凋亡。低浓度的CsA明显增加柔红霉素在HR20细胞内的积聚,其逆转抗药性作用与阻断细胞周期运行无关。CsA10μg·ml^-1处理HR20细胞,可引起50kDa的蛋白质高度磷酸化。结果提示:环孢菌素A阻断抗三尖杉酯碱的HL-60细胞于G₁期,而诱导敏感的HL-60细胞发生凋亡,其阻断作用与抗药性无关。

RETAKDATION OF HUMAN DRUG-RESISTANT HL-60 CELL IN G1 PHASE AND INDUCTON OF SENSITIVE CELL TO APOPTOSIS BY CYCLOSPORINE A

To further study the relationship between resistance to apoptosis and drugresistance in harringtonine-resistant HL-60 cells(HR20),cyclosporine A(CsA)20,10 μg·ml^-1 wasshown to induce the sensitive HL-60 cells to apoptosis,showing a typical DNA“ladder”band.But thesame concentrations of CsA retarded the HR20 cells in G₁ phase and could not induce the cells toapoptosis.The cellular daunorubicin accumulation increased when HR20 cells were treated with lowconcentration of CsA and the reversal of drug resistance by CsA was unrelated to the retardation of cellcycle progression,High phosphorylation of about 50 kDa protein occured when HR20 cells weretreated with CsA 10μg·ml^-1. The results domonstrate that cyclosporine A retarded theharringtonine resistant HL-60 cells in G₁ phase but induced HL-60 cells to apoptosis,and theretardation was unrelated to drug resistance.