Centre for Innovative Research in Medical and Natural Sciences, Faculty of Medicine, University of Rzeszow, Rzeszow, Poland.
Department of Biology and Genetics, Medical University of Lublin, Lublin, Poland.
Oxid Med Cell Longev. 2017;2017:5647281. doi: 10.1155/2017/5647281. Epub 2017 Dec 13.
The presence of multidrug resistance (MDR) in tumor cells is considered as the major cause of failure of cancer chemotherapy. The mechanism responsible for the phenomenon of multidrug resistance is explained, among others, as overexpression of membrane transporters primarily from the ABC family which actively remove cytostatics from the tumor cell. The effect of 20 coumarin derivatives on the cytotoxicity and expression of , , , and genes (encoding proteins responsible for multidrug resistance) in cancer cells was analyzed in the study. The aim of this research included determination of IC10 and IC50 values of selected coumarin derivatives in the presence and absence of mitoxantrone in leukemia cells and analysis of changes in the expression of genes involved in multidrug resistance: , , , and after 24-hour exposure of the investigated cell lines to selected coumarins in the presence and absence of mitoxantrone in IC10 and IC50 concentrations. The designed research was conducted on 5 cell lines derived from the human hematopoietic system: CCRF/CEM, CEM/C1, HL-60, HL-60/MX1, and HL-60/MX2. Cell lines CEM/C1, HL-60/MX1, and HL-60/MX2 exhibit a multidrug resistance phenotype.
肿瘤细胞中存在多药耐药（MDR）被认为是癌症化疗失败的主要原因。多药耐药现象的发生机制除其他外，还可以解释为细胞膜转运蛋白的过度表达，这些蛋白主要来自 ABC 家族，它们可将细胞抑制剂从肿瘤细胞中主动排出。本研究分析了 20 种香豆素衍生物对癌细胞的细胞毒性和 、 、 和 基因（编码多药耐药蛋白）表达的影响。这项研究的目的包括确定在白血病细胞中存在和不存在米托蒽醌时，选定香豆素衍生物的 IC10 和 IC50 值，并分析在选定香豆素衍生物的存在和不存在米托蒽醌的情况下，在 IC10 和 IC50 浓度下，暴露于研究细胞系 24 小时后，参与多药耐药的基因（ 、 、 、 ）的表达变化。设计的研究在 5 个人类造血系统来源的细胞系上进行：CCRF/CEM、CEM/C1、HL-60、HL-60/MX1 和 HL-60/MX2。细胞系 CEM/C1、HL-60/MX1 和 HL-60/MX2 表现出多药耐药表型。
