奥美拉唑增强多柔比星对K562细胞的毒性作用

Oeprazole augments the cytotoxic effect of K562 cells induced by doxorubicin in vitro

目的探讨质子泵抑制剂奥美拉唑增强多柔比星对人白血病细胞系K562的毒性作用。方法奥美拉唑预处理K562细胞0h、24h,MTT法观察多柔比星对K562细胞的毒性作用,计算多柔比星对K562细胞的IC50值。奥美拉唑5μg/ml预处理K562细胞24h后,流式细胞术检测细胞内的多柔比星浓度。结果与无奥美拉唑预处理比较,奥美拉唑(终浓度为1.0、2.0、5.0、10.0μg/ml)预处理0h,多柔比星对K562细胞的IC50值无明显变化;奥美拉唑(终浓度为2.0、5.0、10.0μg/ml)预处理24h,多柔比星对K562细胞的IC50值明显降低(P<0.01);奥美拉唑5μg/ml预处理24h,细胞内多柔比星摄入量有明显增加(P<0.05),且排出量明显降低(P<0.05)。结论奥美拉唑预处理K562细胞,可以增强多柔比星对K562细胞的毒性作用。其机制之一可能是奥美拉唑逆转了细胞的酸性环境,使细胞内发挥作用的多柔比星增多。

Objective To explore the influence of omeprazole, the proton pump inhibitor, on the cytotoxic effects of doxorubiein in human leukemia cell line K562 in vitro. Methods After pretreating K562 cells for 0 or 24 hours with omeprazole, tetrazolium dye （MTT） assay was used to investigate the cytotoxic effects of doxorubicin on K562 cells by calculating the half inhibition concentration （IC50） of doxorubicin against K562 cells. Flow cytometry was used to measure intracellular doxorubicin concentration of K562 cells after treated with omeprazole 5 g/ml（group O） and untreated with omeprazole（group C）. Results Compared with group C, pretreating K562 cells with 1.0,2.0,5.0,10.0 μg/ml omeprazole for 0 hour, the value of IC50 was not significantly different, which was significantly decreased when pretreating K562 cells with 2.0, 5.0, 10. 0 μg/ml omeprazole for 24 hours （P〈0.01）. The doxorubicin intake of the cells was significantly increased and the output significantly decreased when pretreating the cells with omeprazole 5 μg/ml for 24 hours （P〈 0.05）. Conclusion Pretreating K562 cells with omeprazole would enhance the cytotoxic effects of doxorubicin on the K562 cells in vitro. One of the possible mechanisms may be that omeprazole could inverse the acidification of the tumor microenvironment and increase intracellular doxorubicin concentration.