[三氧化二砷对急性早幼粒细胞白血病细胞系中药物转运分子的影响]

[Effect of arsenic trioxide on drug transporting molecules in acute promyelocytic leukemia cell line].

作者信息

Qian Xiao-ping, Liu Bao-rui, Yin Hai-tao, Wang Li-feng, Zou Zheng-yun, Du Juan

机构信息

Department of Oncology, Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing 210008, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2004 Oct;26(10):601-5.

PMID:15634520

Abstract

OBJECTIVE

To study the effect of arsenic trioxide (As2O3) on expression of drug transporting molecules in APL MR2 cell line.

METHODS

MR2 resistant to all-trans retinoic acid (ATRA) and non-ATRA resistant APL cell line NB4 was used in this in vitro study. Expression of P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance-related protein (LRP) was detected by immunocytochemical assay.

RESULTS

The expression of Pgp was significantly higher in MR2 (30%-40%) than in NB4 (10%-20%) (P < 0.001), and that of MRP was also higher in MR2 (56.9 +/- 3.4-21.2 +/- 1.1) than in NB4 (20.6 +/- 5.3-16.7 +/- 1.2) (P < 0.001). As2O3 at concentrations ranging from 0.5 approximately 2.0 micromol/L could significantly decrease the expression of Pgp and MRP, but not that of LRP. The decrease in the expression of Pgp and MRP in MR2 cell line was negatively correlated with the dose and duration of action of As2O3.

CONCLUSION

Pgp and MRP, but not LRP, may be the sensitive targets of As2O3 to overcome drug-resistance. ATRA might be the substrates of Pgp and MRP.

摘要

目的

研究三氧化二砷（As2O3）对急性早幼粒细胞白血病MR2细胞系中药物转运分子表达的影响。

方法

本体外研究使用对全反式维甲酸（ATRA）耐药的MR2以及非ATRA耐药的急性早幼粒细胞白血病细胞系NB4。采用免疫细胞化学分析法检测P-糖蛋白（Pgp）、多药耐药蛋白（MRP）和肺耐药相关蛋白（LRP）的表达。

结果

MR2中Pgp的表达（30%-40%）显著高于NB4（10%-20%）（P<0.001），MR2中MRP的表达（56.9±3.4-21.2±1.1）也高于NB4（20.6±5.3-16.7±1.2）（P<0.001）。浓度范围为0.5至2.0μmol/L的As2O3可显著降低Pgp和MRP的表达，但对LRP的表达无影响。MR2细胞系中Pgp和MRP表达的降低与As2O3的作用剂量和作用持续时间呈负相关。