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The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells
Authors: Jing Shen a; Weijing Zhang a; Jun Wu b; Yunfeng Zhu c
Affiliations: a Affiliated Hospital, Academy of Military Medical Sciences,
b Beijing Institute of Biotechnology, Beijing, China
c Oncology Research Institute, Affiliated Hospital, Academy of Military Medical Sciences,
Abstract
Purpose: This study aimed to evaluate the multidrug resistance (MDR) reversal activity of quercetin (Que) in combination with hyperthermia (HT) in human myelogenous leukemia cells K562/A.
Methods: The cytotoxicity of Que alone and the effect of Que and HT to doxorubicin (Dox) cytotoxicity were determined using MTT assay in K562 and K562/A cells. K562/A cells was heated with or without Que pretreatment, and the protein and mRNA levels of heat shock protein 70 (HSP70) and P-glycoprotein (P-gp) were determined by flow cytometry (FCM) and RT-PCR, respectively.
Intracellular accumulation of Dox, cell cycle and apoptosis were monitored with FCM.
Results: Que alone inhibited cell growth in a dose-dependent manner in K562 and K562/A cells. Either Que or HT alone had a weak reversal effect on Dox resistance, however, combination HT and Que showed a much more significant reversal effect on Dox resistance (reverse fold 9.49).
The elevated protein expression and mRNA level of HSP70 and P-gp in response to HT were inhibited by Que. Pretreatment with Que caused the cells to accumulate Dox 8.3-fold higher than in control cells.
In addition, Que induced apoptosis and G2/M arrest in a dose-dependent manner, and the combination of Que and HT was found to have a synergistic efeect on apoptosis.
Conclusions: Que pretreatment could significantly inhance the MDR reversal activity of HT in resistant cell line, by sensitizing the cell to reversing MDR activity of HT.
DOI: 10.1080/02656730701843109
International Journal of Hyperthermia, Volume 24, Issue 2 2008 , pages 151 - 159
First Published on: 14 January 2008
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