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Int J Hyperthermia. 2008 Mar;24(2):151-9. doi: 10.1080/02656730701843109.

The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells.

Author information

1
Affiliated Hospital, Academy of Military Medical Sciences, Beijing, China.

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 effect on apoptosis.

CONCLUSIONS:

Que pretreatment could significantly enhance the MDR reversal activity of HT in resistant cell line, by sensitizing the cell to reversing MDR activity of HT.

PMID:
18283591
DOI:
10.1080/02656730701843109
[Indexed for MEDLINE]

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