MDR1 and Cytochrome P450 Gene-Expression Profiles as Markers of Chemosensitivity in Human Chronic Myelogenous Leukemia Cells Treated with Cisplatin and Ru(III) Metallocomplexes
MDR1 and Cytochrome P450 Gene-Expression Profiles as Markers of Chemosensitivity in Human Chronic Myelogenous Leukemia Cells Treated with Cisplatin and Ru(III) Metallocomplexes
复制标题
DOI：
10.1007/s12011-014-0133-2
复制
发表时间：
2015-02-01
影响因子：
3.9
通讯作者：
Silveira-Lacerda, Elisangela de Paula
中科院分区：
文献类型：
--
作者：
Sam Tiago Vilanova-Costa, Cesar Augusto;Paes Porto, Hellen Karine;Silveira-Lacerda, Elisangela de Paula
白血病是一种主要的癌症类型，影响着相当大一部分人群，尤其是儿童。事实上，白血病是最常见的儿童癌症，占所有病例的26%，死亡率为20%。多药耐药表型（MDR）被认为是癌症化疗失败的主要原因之一。本研究旨在探讨用顺铂（cisPt）以及两种基于钌的配合物[顺式CRu(III)和顺式DRu(III)]处理的人慢性髓性白血病细胞（K - 562）中MDR1和CYP450基因表达之间的关系。所测试的化合物诱导了K - 562肿瘤细胞的凋亡，这通过半胱天冬酶3的激活得以证明。结果还显示，暴露于顺铂和顺式CRu(III)的K - 562细胞中P - gp基因的扩增比暴露于顺式DRu(III)的细胞更大。综上所述，所有这些结果有力地表明，K - 562细胞中MDR - 1的过度表达可能与多药耐药表型有关，而且它也导致了这些细胞对铂及结构相关化合物的耐药性。
Leukemia is a major type of cancer affecting a significant segment of the population, and especially children. In fact, leukemia is the most frequent childhood cancer, with 26 % of all cases, and 20 % mortality. The multidrug resistance phenotype (MDR) is considered one of the major causes of failure in cancer chemotherapy. The present study aimed to investigate the relationship between the expression of MDR1 and CYP450 genes in human chronic myelogenous leukemia cells (K-562) treated with cisplatin (cisPt) and two ruthenium-based coordinated complexes [cisCRu(III) and cisDRu(III)]. The tested compounds induced apoptosis in K-562 tumor cells as evidenced by caspase 3 activation. Results also revealed that the amplification of P-gp gene is greater in K-562 cells exposed to cisPt and cisCRu(III) than cisDRu(III). Taken together, all these results strongly demonstrate that MDR-1 overexpression in K-562 cells could be associated to a MDR phenotype, and moreover, it is also contributing to the platinum and structurally related compound, resistance in these cells.