【摘要】 目的:研究放线菌素D对沙尔威辛诱导K562细胞凋亡和细胞毒性的影响。方法:采用四氮唑盐(MTT)还原法测定药物对K562细胞的生长抑制作用;凋亡诱导作用采用荧光显微镜术、DNA琼脂糖凝胶电泳和流式细胞术进行评价。结果:药物处理K562细胞24h后检测发现,放线菌素D能在一定程度上增强沙尔威辛6.25μmol/L的细胞毒性作用,平均生长抑制率由沙尔威辛单独应用时8％上升到联合应用放线菌素D 0.04、0.4和4μmol/L时的69％、71％和70％。在沙尔威辛浓度大于6.25μmol/L时,未见同样的增强作用,却也不减弱其抑制细胞生长的作用。这显示放线菌素D可以增强或至少不减弱沙尔威辛的细胞毒性作用。但荧光显微镜 术、DNA琼脂糖凝胶电泳和流式细胞术却表明,在同等条件下,放线菌素D抑制沙尔威辛诱导K562细胞凋亡。结论:放线菌素D可增强沙尔威辛适当浓度范围内的细胞毒性作用,但却抑制其诱导的白血病细胞凋亡,提示该过程中存在着除凋亡以外的其它细胞死亡方式。更多还原

【Abstract】 AIM: To study the effects of actinomycin D(Act D) on the cytotoxicity and apoptosis elicited by salvicine in human leukemia K562 cells. METHODS: Growth inhibition of K562 cells was measured by the microculture tetrozolium(MTT) assay. Cell apoptosis was evaluated by fluorescence microscopy, DNA agarose gel electrophoresis, and flow cytometry. RESULTS: Following exposure of K-562 cells to salvicine plus Act D for 24 h, Act D at the concentrations of 0.04, 0.4, and 4μmol/L potentiated the cytotoxicity of salvicine 6.25μmol/L to some degree. The mean growth inhibitory rates went from 8% up to 69%, 71%, and 70%, respectively. However, the same enhancement of Act D did not continue to emerge at the higher concentrations than salvicine 6.25μmol/L. Act D enhanced, or at least, did not decrease the cytotoxicity of salvicine against K562 cells. Fluorescence microscopy, DNA agarose gel electrophoresis, and flow cytometry revealed that Act D concentration-dependently inhibited the induction of apoptosis by salvicine in the same cell line. CONCLUSION: The combination of salvicine and Act D in a proper range of concentrations is able to enhance the cytotoxicity of salvicine against K562 cells though inhibiting apoptosis. The other mechanisms of cell death except apoptosis may be implicated in the process.更多还原