Effects of quercetin on multidrug resistance and expression of related genes in human erythroleukemic K562/a cells / 中国实验血液学杂志

ABSTRACT

The study was aimed to investigate the effect of quercetin, flavonoid molecules on reversing leukemia multidrug resistance and its mechanism. K562/A cells were cultured in vitro with different concentrations of quercetin. Cell growth inhibition and adriamycin (ADR) sensitivity were detected by MTT method. Intracellular ADR concentration was determined by flow cytometry. Cell apoptosis was assayed by Annexin V/PI staining method. The expressions of drug transporter and apoptosis related genes were measured by real-time PCR array. The results indicated that quercetin inhibited the proliferation of K562 and K562/A in 5-160 µmol/L and with dose-dependent manner. Quercetin increased the sensitivity of K562/A cells to ADR in a low toxicity concentration. Flow cytometry showed that the quercetin increased the accumulation of ADR in K562/A cells when cells were co-cultured with 5 µmol/L ADR for 2 hours. Quercetin could induce the apoptosis of K562 and K562/A cells with dose dependent manner. Furthermore, some drug transport related genes such as ATP-binding cassette (ABC) and solute carrier (SLC) and some apoptosis-related genes such as BCL-2, tumor necrosis factor (TNF), tumor necrosis factor receptor (TNFR) families were down-regulated by quercetin. It is concluded that quercetin reverses MDR of leukemic cells by multiple mechanisms and the reversing effect is positively related to drug concentration.