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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 investigate the toxic effects of proton pump inhibitor omeprazole on doxorubicin-induced human leukemia cell line K562. Methods Omeprazole pretreatment K562 cells 0h, 24h, MTT assay of doxorubicin on K562 cells toxicity, calculate the IC50 value of doxorubicin on K562 cells. Omeprazole 5μg / ml pretreated K562 cells 24h, flow cytometry intracellular doxorubicin concentration. Results Compared with no omeprazole pretreatment, the IC50 values of doxorubicin on K562 cells had no significant change after pretreatment with omeprazole (1.0, 2.0, 5.0 and 10.0 μg / ml) for 0 h. Ogilvy, The IC50 values of doxorubicin in K562 cells were significantly decreased (P <0.01) after preconditioning with pirarubone (2.0, 5.0 and 10.0 μg / ml) for 24 h. Pretreatment with omeprazole 5 μg / ml for 24h Doxorubicin intake was significantly increased (P <0.05), and the discharge was significantly reduced (P <0.05). Conclusion Omeprazole pretreatment K562 cells, can enhance the toxicity of doxorubicin on K562 cells. One of the mechanisms may be that omeprazole reverses the acidic environment of cells and increases the amount of doxorubicin in the cell.