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槲皮素和山柰酚逆转白血病细胞系K562/A02多药耐药性的机制及相关基因表达谱的研究

OBJECTIVE To investigate the possibility and mechanism of quercetin and kaempferol， flavonoid molecules， for reversing multidrug resistance (MDR in K562/A02 cells. METHODS K562 and K562/A02 cells were cultured in vitro with the flavonoids as single and in combination respectively. Cell growth inhibition and adriamycin (ADM sensitivity were detected by MTT assay. Intracellular ADM concentration was determined by flow cytometry when K562/A02 cells was cultured with ADM and the flavonoids for 2 h. Cell apoptosis was examined by Annexin V/PI staining method. Moreover， the expression of related genes for drug transporters and apoptosis was also tested by real time PCR array. RESULTS The MTT assay showed that quercetin and keampferol inhibited the proliferation of K562 and K562/A02 at the concentrnation of 5-160 mol·L-1. They also increased the sensitivity of K562/A02 cells to ADM at a low toxicity concentration. Flow cytometry showed quercetin increased intracellular ADM in a dose dependent manner. but keampferol showed trivial effect on intracellular ADM accumulation. However， quercetin+keampferol treatment showed a similar effect to that of quercetin alone. Cell apoptosis experiment showed both compounds had a dose dependent effect on K562 and K562/A02 cells. Furthermore， PCR array showed that some of the genes related to drug transporters such as ATP-binding cassette(ABC and solute carrier(SLC and some of the genes related to apoptosis such as Bcl-2， TNF and TNFR families were regulated. CONCLUSION The experiment indicated that quercetin and kaempferol may be used as reveratrol in leukemia chemotherapy， but their interaction and difference should be noticed.