mTOR信号转导通路与三氧化二砷反应关联的研究

Correlation between mTOR Signaling Transduction Pathway and Arsenic Trioxide Response

本研究探讨三氧化二砷(ATO)作用与mTOR信号通路的联系。应用Western blot方法检测K562/DNR细胞经ATO处理不同时间后细胞中pmTOR、pAKT及pP70S6K的表达;应用流式细胞术检测K562/DNR细胞经ATO联合LY294002或雷帕霉素处理120小时后细胞的凋亡率。结果表明:K562/DNR细胞经ATO处理60分钟及120分钟时pmTOR表达高于对照组(p<0.01);经ATO处理30分钟及60分钟时pAKT表达高于对照组(p<0.01);经ATO处理60分钟时pP70S6K表达高于对照组(p<0.01)。K562/DNR细胞经ATO联合LY294002或雷帕霉素处理后细胞凋亡率高于对照组(p<0.01)。结论:K562/DNR细胞经一定浓度的ATO处理后细胞中mTOR信号通路被激活;mTOR信号通路抑制剂可增强ATO触发K562/DNR细胞凋亡的作用。

This study was aimed to investigate the correlation between mTOR signaling transduction pathway and arsenic trioxide （ATO） effect, The expressions of pmTOR, pAKT and pP70S6K in K562/DNR treated with ATO for different time were detected by Western blot. The apoptosis rate of K562/DNR treated by ATO combined with LY294002 or rapamycin for 120 hours was assayed by flow cytometry. The results showed that the expression of pmTOR in K562/DNR cells treated with ATO for 60 minutes or 120 minutes was higher than that in the control group （p 〈 0.01 ） ; the expressions of pAKT in the cells treated with ATO for 30 minutes or 60 minutes were higher than that in the control group（p 〈0.01 ） ; the expression of pPTOS6K in the cells treated with ATO for 60 minutes was higher than that in the control group（p 〈 0.01 ）. The apoptosis rate of K562/DNR cells treated with combination of ATO and LY294002 or rapamycin were higher than that in the control group. It is concluded that the mTOR signaling pathway in K562/DNR cells is activated by a certain concentration of ATO, and mTOR signaling pathway inhibitors enhance ATO to trigger apoptosis in K562/DNR cells.