Effects of iron deprivation on multidrug resistance of leukemic K562 cells.

Abstract

BACKGROUND AND AIM Multidrug resistance (MDR) compromises the efficacy of chemotherapy. Many approaches have been used to reduce MDR; however, the results are poor. It has been reported that iron deprivation downregulates MDR genes. To investigate the relationship of iron with MDR and early growth response gene-1 (EGR1), we investigated the effect of iron deprivation on expression and/or function of multidrug resistance-1 (MDR1), early growth response gene-1 (EGR1), ferritin heavy chain gene (H-Fn) and MDR1-encoded P-glycoprotein (P-gp) in the K562 leukemic cell line. METHODS The cells were stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) and incubated with either FeCl(3) or the iron-chelating drug DFO. The mRNA levels of MDR1, EGR1 and H-Fn were detected by RT-PCR. The protein expression and function of P-gp were measured by immunohistochemical staining and flow cytometry, respectively. RESULTS DFO significantly reduced the intracellular iron level, and led to approximately 70% reduction of MDR1 mRNA, approximately 50% of reduction of H-Fn mRNA and approximately 30% reduction of P-gp protein in TPA-differentiated K562 cells. The P-gp pump function, measured by daunorubicin exclusion, was also reduced by DFO treatment. CONCLUSIONS These results suggest a close relationship between iron deprivation and reduced MDR1/P-gp expression and function. DFO may be used together with chemotherapeutic drugs to achieve better clinical efficacy.

DOI: 10.1159/000287352

Cite this paper

@article{Fang2010EffectsOI, title={Effects of iron deprivation on multidrug resistance of leukemic K562 cells.}, author={Dingzhu Fang and Yixiao Bao and Xiaobin Li and Fang Liu and Kang Cai and J. Gao and Qingkui Liao}, journal={Chemotherapy}, year={2010}, volume={56 1}, pages={9-16} }