MDR-1与GST-π在柔红霉素诱导Kasumi-1细胞耐药中的作用  

Roles of MDR-1 and GST-π in Drug Resistance of AML-M2 Cell Line Kasumi-1 Induced by Daunorubicin

作　　者：张洁[1] 李娜[1] 千新来[1] 

机构地区：[1]新乡医学院病理学教研室,新乡453003

出　　处：《医药导报》2013年第8期1015-1017,共3页Herald of Medicine

摘　　要：目的探讨柔红霉素诱导M2型急性髓系白血病(AML-M2)细胞株Kasumi-1耐药性与多药耐药基因-1(MDR-1)和谷胱甘肽S转移酶-π(GST-π)表达的相关性。方法长期间歇性小剂量递增法诱导Kasumi-1对柔红霉素耐药,四氮唑蓝(MTT)法检测细胞耐药程度;实时定量聚合酶链反应(RT-PCR)检测MDR-1和GST-π基因表达变化情况;Western blot检测P-糖蛋白(P-gp)和GST-π蛋白表达的变化情况。结果诱导后Kasumi-1对柔红霉素耐药倍数为(3.9±0.6)倍,耐药细胞与非耐药细胞MDR-1表达无明显差别,耐药细胞GST-π表达明显高于非耐药细胞(P<0.01)。Western blot检测结果与RT-RCR一致,两种细胞P-gp表达情况无明显差异,耐药株GST-π蛋白表达明显升高(P<0.01)。结论 AML-M2细胞株Kasumi-1对柔红霉素耐药与MDR-1表达无关,与GST-π表达有关,抑制GST-π在Kasumi-1细胞中的表达可能成为逆转柔红霉素耐药的靶点。Objective To explore the relationship of daunorubicin （DNR） resistance and MDR-1, GST-π in acute myeloid leukemia cell lines Kasumi-1. Methods The DNR-resistant human acute myeloid leukemia cell line （Kasumi-1/ DNR） was established with exposure to DNR. MTT assay was used to detect the drug sensitivity of Kasumi-1 and Kasumi-1/DNR ceils. RT-PCR was used to detect the MDR-1 and GST-π mRNA expression. Western blotting was used to observe the P-gp and GST-π expression. Results It was found that MDR-1 mRNA expression in Kasumi-1 was the similar as the Kasumi-1/DNR, but the GST-π mRNA expression in Kasumi-1 was lower than Kasumi-1/DNR. The protein expression was consistent with mRNA expression. Conclusion GST-π but not MDR-1 is related directly with DNR resistance in Kasumi-1/DNR. GST-π inhibitors may improve the clinical efficacy of DNR.

关 键 词：柔红霉素 耐药 KASUMI-1 多药耐药基因-1 谷胱甘肽S转移酶-Π 

分 类 号：R979.1[医药卫生—药品] R965[医药卫生—药学]