柔红霉素在HL-60ADR细胞内的异常分布

Altered subcellular distribution of daunorubicin in the non P-glycoprotein mediated multidrug resistant cell line HL-60/ADR

目的 了解化疗药物在非Pgp耐药细胞株HL 6 0 ADR细胞内的异常分布与耐药的关系。方法 采用共聚焦激光扫描显微镜观察、荧光染色、MTT、逆转录 聚合酶链反应 (RT PCR)等方法研究柔红霉素 (DNR)在HL 6 0 ADR细胞内的分布及与耐药的关系 ,以及维拉帕米、布雷菲尔得菌素、氯喹对细胞内DNR异常分布的影响。结果 与DNR在HL 6 0细胞核、胞浆均匀分布不同 ,在HL 6 0 ADR ,DNR呈点棘状分布于细胞浆外周区 ,核内DNR荧光很少 ;维拉帕米、布雷菲尔得菌素可逆转DNR在HL 6 0 ADR的异常分布 ,而氯喹无此作用。结论 DNR在耐药细胞的异常分布与肿瘤细胞耐药的形成有关。

Objective To investigate DNR subcellular distribution in the non P glycoprotein mediated multidrug resistant cell line HL 60/ADR and its relation to multidrug resistance. Methods DNR subcellular disposition was studied by confocal scanning laser microscopy, fluorescent methods, MTT and RT PCR. The effects of verapamil, brefeldin A, chloroquine were also examined. Results In the drug sensitive cell line HL 60 DNR fluorscence distributed evenly in the nucleus and cytoplasm, while in the resistant cell line DNR distributed in a punctate pattern in the cytoplasm and was reduced in the nucleus. Verapamil, brefeldin A, but not chloroquine could recover the intracellular distribution of DNR from punctate to even in the resistant cell line. Conclusion Altered subcellular disposition of DNR in resistant cell line was involved in the mechanism of multidrug resistance.