[Reversal effect of nuclear factor-κB protease inhibitor PDTC on multidrug resistance of K562/AO₂ cells and its mechanism].
Journal: 2011/September - Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology
ISSN: 1009-2137
PUBMED: 20723297
Abstract:
This study was purposed to investigate the relationship between activation of nuclear factor-κB (NF-κB) and multidrug resistance in K562/AO₂ cells and its mechanism. Human erythroleukemic cell line K562 and its adriamycin-resistant counterpart K562/AO₂ cells were used in the study. After inhibiting the activation of NF-κB with noncytotoxic concentration of antioxidant pyrrolidine dithiocarbamate (PDTC) in vitro, the multiple of drug resistance of K562/AO₂ cells was assessed by MTT assay. RT-PCR and flow cytometry method were used to detect the relative expression of mdr-1 mRNA and P-gp, respectively. The results showed that (1) multidrug resistance of K562/AO₂ cells to ADM was 59 times higher than that of K562 cells. When being pretreated with 0.2 μmol/L PDTC which is noncytotoxic to cells, the IC₅₀ of ADM in K562/AO₂ cells was sharply decreased with relative reverse efficiency of 93.03%, which was more higher than that of classic modifying agents Verapamil (Ver); (2) NF-κB activity of K562/AO₂ cells was significantly higher than that of K562 cells (p < 0.01). When being treated with PDTC, the activation of NF-κB was sharply decreased in K562/AO₂ cells; with 0.2 μmol/L PDTC for 24 hours it decreased to the lowest, nearly to the K562 cell level (p>> 0.05); (3) the relative expression of both mdr-1 mRNA and P-gp in K562/AO₂ cells was more higher; the expressions of mdr-1 mRNA and P-gp both were inhibited in K562/AO₂ cell group treated with PDTC for 48 hours. It is concluded that the PDTC used as an inhibitor of NF-κB activity can partially reverse the multidrug resistance of K562/AO₂ cells, which mechanism can be associated with the down-regulation of mdr-1 mRNA and P-gp.
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