环孢素A对THP-1细胞的增敏作用及与多药耐药相关蛋白-1的关系
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The relationship of chemotherapy sensitization to THP-1 cells by cyclosporin A with multidrug resistance associated protein-1
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    目的:观察环孢素A(CsA)处理急性单核细胞白血病细胞株THP-1后对柔红霉素(DNR)的耐药性及与多药耐药相关蛋白-1(MRP1)表达的关系,探讨CsA对THP-1细胞的化疗增敏作用及相关机制-方法:噻唑蓝(MTT)法-荧光分光光度法-共聚焦激光扫描显微镜(CLSM)法分别检测CsA处理前后50%THP-1细胞生长受抑的DNR浓度(IC50)-THP-1细胞内DNR含量及分布的变化-免疫细胞化学法-Western blot法检测CsA处理前后THP-1细胞MRP1蛋白表达量的变化-结果:CsA处理后THP-1细胞的IC50明显下降(1.536 4 ± 0.175 1 vs 0.558 8 ± 0.054 7,P < 0.01),细胞内DNR含量明显增加(21.40 ± 1.71 vs 131.96 ± 16.45,P < 0.01),且胞浆内分布更加均匀;同时MRP1蛋白表达量增高(0.266 5 ± 0.004 2 vs 0.316 9 ± 0.006 2,P < 0.01)-结论:CsA可增加THP-1细胞对DNR的敏感性,降低其耐药性,并提示CsA对THP-1细胞耐药性的改变不是通过降低其MRP1蛋白表达量来实现的-

    Abstract:

    Objective:To observe the changes of resistance to daunorubicin(DNR) and the expression of multidrug resistance associated protein-1(MRP1) in acute monocytic leukemia cells THP-1 treated by cyclosporin A(CsA), and explore CsA’s function on chemotherapy sensitization to THP-1 cells as well as the related mechanism. Methods:IC50 of DNR to THP-1 cells, content and distribution of DNR in THP-1 cells treated by CsA were examined by MTT method and confocal laser scanning microscopy method, respectively. Expression amount of MRP1 were detected by immunocytochemistry and Western blot. Results:After treated with CsA, IC50 decreased obviously(1.536 4 ± 0.175 1 vs 0.558 8 ± 0.054 7,P < 0.01), content of DNR increasing obviously(21.40 ± 1.71 vs 131.96 ± 16.45,P < 0.01), DNR distributing uniformly,and expression of MRP1 increased(0.266 5 ± 0.004 2 vs 0.316 9 ± 0.006 2,P < 0.01). Conclusion:CsA can increase the sensibility of THP-1 cells to DNR, not through decreasing the expression of MRP1 in THP-1 cells. This might show that the resistance of THP-1 cells to DNR can’t be reduced by inhibiting the activity of MRP.

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葛群芳,陈建斌,汤为学,廖 洋,卢前微,杨泽松.环孢素A对THP-1细胞的增敏作用及与多药耐药相关蛋白-1的关系[J].南京医科大学学报(自然科学版),2009,29(8):1071-1076

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  • 收稿日期:2009-02-19
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