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Assessment of Multidrug Resistance Reversal Using Dielectrophoresis and Flow Cytometry

机译:介电电泳和流式细胞术评估多药耐药性逆转

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摘要

In cancer, multidrug resistance (MDR) is the simultaneous resistance of tumor cells to different natural product anticancer drugs that have no common structure. This is an impediment to the successful treatment of many human cancers. A common correlate of MDR is the overexpression of a membrane protein, P-glycoprotein. Many studies have shown that MDR can be reversed after the use of substrate analogs, called MDR modulators. However, our understanding of MDR modulation is incomplete. In this article, we examine the electrical properties of the human leukemic cells (K562) and its MDR counterpart (K562AR) using dielectrophoresis and flow cytometry (with a membrane potential sensitive dye, DIOC5), both before and after treatment with XR9576 (a P-glycoprotein-specific MDR-reversal agent). The results show significant differences in the cytoplasmic conductivity between the cell lines themselves, but indicate no significant changes after modulation therapy. We conclude that the process of MDR modulation is not associated with changes in the electrical properties of cancer cells. Moreover, the results demonstrate that using the flow cytometry method alone, with MDR cells, may produce artifactual results—whereas in combination with dielectrophoresis, the results show the role of MDR modulators in preventing drug efflux in MDR cells.
机译:在癌症中,多药耐药性(MDR)是肿瘤细胞对没有共同结构的不同天然产物抗癌药的同时耐药性。这是成功治疗许多人类癌症的障碍。 MDR的常见关联是膜蛋白P-糖蛋白的过表达。许多研究表明,使用称为MDR调节剂的底物类似物可以逆转MDR。但是,我们对MDR调制的理解还不完整。在本文中,我们使用介电电泳和流式细胞仪(带有膜电位敏感染料DIOC5),在用XR9576处理前和后,检查了人类白血病细胞(K562)及其MDR对应物(K562AR)的电学性质。 -糖蛋白特异性MDR逆转剂)。结果表明,细胞系之间的细胞质电导率存在显着差异,但表明调制疗法后无明显变化。我们得出结论,MDR调节过程与癌细胞电特性的变化无关。此外,结果表明,单独使用流式细胞仪方法对MDR细胞可能会产生假象结果,而与介电电泳相结合,结果表明MDR调节剂在预防MDR细胞中药物外排中的作用。

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