The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells
The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells
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DOI：
10.1080/02656730701843109
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Yunfeng Zhu
中科院分区：
文献类型：
--
作者：
Jing Shen;Weijing Zhang;Yunfeng Zhu
目的：本研究旨在探讨槲皮素（Que）联合热疗（HT）对人髓性白血病细胞株K562/A多药耐药（MDR）的逆转作用。方法：采用MTT法检测Que单药对K562和K562/A细胞的细胞毒作用以及Que和HT对阿霉素（Dox）细胞毒作用的影响。采用流式细胞术（FCM）和RT-PCR方法分别检测Que预处理前后K562/A细胞热休克蛋白70（HSP 70）和P糖蛋白（P-gp）的蛋白和mRNA表达水平。结果：Que单独作用于K562和K562/A细胞，呈剂量依赖性地抑制细胞生长; Que或HT单独对Dox抗性具有弱的逆转作用，然而，HT和Que组合对Dox抗性显示出显著得多的逆转作用（逆转倍数9.49）。Que可抑制HT诱导的HSP 70和P-gp蛋白表达和mRNA水平的升高。用Que预处理导致细胞积累比对照细胞高8.3倍的Dox。结论：Que预处理可明显增强HT对耐药细胞的MDR逆转活性，其机制可能与Que对HT的敏感性有关。
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.