ABSTRACT
Chemotherapy may be followed by multiple drug resistance (MDR). This is an obstacle in the treatment of cancer. It is therefore essential to understand the mechanisms underlying tumor resistance, especially those involved in the cell target/MDR relationship. To investigate this, the effects of exposing cells to UVB (to target DNA), UVA, and H2 O2 (to target the cell membrane) were observed in K562 (non MDR) and FEPS (MDR) cell lines. The K562 cells were more sensitive to UVA than the FEPS cells. The FEPS cell line was more resistant to H2 O2 than K562, only presenting cytotoxicity 72 h after being exposed to 40 mM, with no ROS increase until 48 h. Both cell lines were sensitive to UVB, presenting cytotoxicity after 24 h, mainly by apoptosis, and showed an increase in ROS levels. Our results indicate that agents acting on DNA may be able to overcome the MDR phenotype.
Subject(s)
Apoptosis/drug effects , Drug Resistance, Neoplasm , Hydrogen Peroxide/pharmacology , Ultraviolet Rays , Apoptosis/radiation effects , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Humans , K562 Cells , Leukemia, Erythroblastic, Acute/metabolism , Leukemia, Erythroblastic, Acute/pathology , Phenotype , Reactive Oxygen Species/metabolismABSTRACT
The gene expression of Oct-4, a transcription factor and hematopoietic stem cell marker, is higher in Lucena lines, which is MDR, and the gene Alox-5 has also been implicated in the differentiation of some cell lines. The aim of this study was to compare the response to PMA-induced differentiation in MDR and non-MDR cells. We observed the differentiation to megakaryocytes in the K562 cell line, which is non-MDR. The expression of Alox-5 and Nanog genes was downregulated and that of Mdr-1 was upregulated in K562 cells. The Lucena cell line contained a higher number of megakaryocytes than the non-MDR, but this number was not altered by PMA, as well as Mdr-1 gene expression. However, Alox-5 expression was downregulated. Alox-5, Mdr-1, Nanog, Oct-4 and Sox-2 basal expression was also evaluated in the K562, Lucena and FEPS (also MDR) cell lines. The transcription factors gene expression was similar in MDR cell lines. The expression of Alox-5 was higher in the non-MDR cell line, while FEPS had the lowest expression of this gene. The opposite pattern was observed for Mdr-1 gene expression. These results suggest that the Alox-5 gene might play a role in the differentiation of these cell lines.
