环氧合酶-2抑制剂联合苦参碱逆转K562/AO2细胞多药耐药的研究-东南大学学报医学版

环氧合酶-2抑制剂联合苦参碱逆转K562/AO2细胞多药耐药的研究

单位：1. 东南大学医学院附属蚌埠第三人民医院血液科, 安徽蚌埠 233000;
2. 东南大学附属中大医院血液科, 江苏南京 210009

分类号：R-331; R969.2

出版年·卷·期（页码）：2012·31·第二期（174-178）

摘要：

目的:研究塞来昔布单独及联合应用苦参碱对K562/AO2细胞多药耐药逆转作用的影响,以及探讨他们互相作用的机理。方法:采用四甲基偶氮唑盐(MTT)法检测阿霉素(ADM)的半数抑制量;流式细胞术检测细胞凋亡;RT-PCR方法检测多药耐药基因(MDR)和环氧合酶-2(COX-2)mRNA的表达水平;Western blotting方法检测人p-糖蛋白(P-gp)和COX-2蛋白的表达水平。结果:ADM对K562、K562/AO2细胞的IC₅₀值分别为0.398、33.31 μg·ml^-1;苦参碱(200 μg·ml^-1)、塞来昔布(7.5 μg·ml^-1)单独及联合应用处理细胞时,ADM对K562/AO2细胞的IC₅₀值分别为9.44、12.84、2.71 μg·ml^-1;苦参碱、塞来昔布单独及联合应用于K562/AO2细胞后凋亡率明显增加,MDR1和COX-2 mRNA以及P-gp、COX-2蛋白的表达明显下调,且两药联合时下调更明显。结论:苦参碱和塞来昔布均有逆转K562/AO2细胞多药耐药的作用,两药联合应用时效果更加明显,P-gp的高表达可能与COX-2的表达上调有关。

Objective: To investigate the effect of celecoxib alone and in combination with matrine on multidrug resistance of K562/AO2 cell line,and to explore the mechanism of their interaction. Methods: We use the methyl blue tetrazolium(MTT) assay to detect half the amount of adriamycin(ADM). We have the detection of apoptosis by flow cytometry. We use RT-PCR to detect multidrug resistance(MDR) gene MDR1 and cyclooxygenase-2(COX-2) mRNA expression levels. We detected permeability glycoprotein(P-gp) and COX-2 protein expression by Western blotting. Results: ADM for K562, K562/AO2 the IC₅₀ values were 0.398, 33.31 μg·ml^-1. When matrine (200 μg·ml^-1), celecoxib (7.5 μg·ml^-1) alone and in combination-treated cells, the IC₅₀ values of ADM for K562/AO2 were 9.44, 12.84, 2.71 μg·ml^-1. Matrine, celecoxib alone or jointly used, K562/AO2 cell apoptosis was significantly increased, MDR1 and COX-2 mRNA and P-gp, COX-2 protein expression was significantly reduced. And the two-drug combination was significantly reduced. Conclusion: Matrine and celecoxib can reverse resistant K562/AO2 role, and when two drugs in combination was more evident. And high expression of P-gp may be associated with upregulation of COX-2.

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