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[粉防己碱、托瑞米芬及其联合应用对K562/A02细胞株多药耐药逆转的影响]

[Effect of tetrandrine, toremifene and their combination on the reversion of multidrug resistance of K562/A02 cell line].

作者信息

Zhao Qiu-Xia, Chen Bao-An, Cheng Jian, Ding Jia-Hua, Gao Feng, Gao Chong, Sun Yun-Yu, Wang Jun, Zhao Gang, Bao Wen, Song Hui-Hui

机构信息

Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical College, Nanjing 210009, Jiangsu Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Feb;16(1):61-4.

Abstract

This study was aimed to investigate the reversible effect of tetrandrine, toremifene and their combination on multidrug resistance of K562/A02 cell line. The IC(50) (the concentration causing 50% inhibition of cell growth) of adriamycin (ADR) were assayed by MTT method, the expression of MDR1 mRNA was measured by RT-PCR, the concentration of p-glycoprotein (P-gp) and intracellular ADR were detected by flow cytometry. The results showed that the IC(50) of ADR on K562/A02 and K562 cells were 57.43 and 1.16 mg/L, respectively. The IC(50) of ADR on K562/A02 cells after treatment with tetrandrine, toremifene and both combination were 14.12, 20.74 and 9.14 mg/L respectively, but both drugs did not influence the IC(50) of ADR on K562 cells. Pretreating K562/A02 cells with toremifene (2.5 micromol/L), tetrandrine (1 micromol/L) or both for 72 hours partially restored the sensitivity of K562/A02 cells to ADR. Tetrandrine and toremifene (alone or combination) elevated the ADR concentration in K562/A02, down regulated the expressions of P-gp and MDR1 mRNA. It is concluded that multidrug resistance of K562/A02 cells can be partially reversed by tetrandrine or toremifene, the combination of both drugs shows a higher synergistic reversal effect.

摘要

本研究旨在探讨粉防己碱、托瑞米芬及其联合应用对K562/A02细胞系多药耐药性的逆转作用。采用MTT法检测阿霉素(ADR)的IC50(导致细胞生长抑制50%的浓度),采用RT-PCR法检测MDR1 mRNA的表达,采用流式细胞术检测P-糖蛋白(P-gp)浓度和细胞内ADR浓度。结果显示,ADR对K562/A02和K562细胞的IC50分别为57.43和1.16 mg/L。粉防己碱、托瑞米芬及其联合处理后,ADR对K562/A02细胞的IC50分别为14.12、20.74和9.14 mg/L,但两种药物均不影响ADR对K562细胞的IC50。用托瑞米芬(2.5 μmol/L)、粉防己碱(1 μmol/L)或两者预处理K562/A02细胞72小时,可部分恢复K562/A02细胞对ADR的敏感性。粉防己碱和托瑞米芬(单独或联合应用)可提高K562/A02细胞内ADR浓度,下调P-gp和MDR1 mRNA的表达。结论:粉防己碱或托瑞米芬可部分逆转K562/A02细胞的多药耐药性,两者联合应用显示出更高的协同逆转作用。

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