环孢菌素A逆转白血病多药耐药机制的实验研究

EXPERIMENTAL STUDY ON REVERSAL MECHANISM OF MULTIDRUG RESISTANCE BY CYCLOSPORINE A

目的 :研究环孢菌素 A(Cs A)持续作用 7天后 ,K5 6 2 /AO2细胞多药耐药性的变化及其变化机制。方法 :细胞毒性试验采用 MTT法 ,细胞内柔红霉素 (DNR)浓度用流式细胞术检测 ,多药耐药基因 (m dr1)的表达水平用 RT- PCR方法检测。结果 :K5 6 2 /AO2耐药性降低 2 .2倍 ,K5 6 2 /AO2细胞内 DNR浓度明显升高 ,mdr1表达降低 ,佛伯酯 (TPA )可拮抗 Cs A升高细胞的 DNR浓度的作用。结论 :Cs A可下调 mdr1的表达和细胞内 DNR浓度进而逆转 MDR,其作用可能与 Cs A抑制蛋白激酶 D(PKC)

Objective:To investigate the variation of multidrug resistance (MDR) in K562/AO2 cells after the sustaining affection on K562/AO2 cells by cyclosporine A.Methods:Cytotoxic effect was assayed by MTT method after K562/AO2 cells were cultured in CsA-containing medium for 7 days.Flow cytometry was used to mersured the intracellular daunorubicin concentration.The expression of MDR gene was analysied by RT-PCR method.Rusults:The sensitivity of to K562/AO2 cells to DNR increased by about 2 times with the increasing of intracellular DNR concentration which can be antagonized by phorbol ester (TPA) and the decreasing of mdr1 gene expression.Conclusion:CsA could reverse the MDR in K562/AO2 cells by down-regulation the expression of mdr1 gene and increasing the intracellular drug concentration.These might be contributed to it's inhibiting effect on protein kinase C(PKC) activity.