论文部分内容阅读
目的:研究青蒿素衍生物二蒿乙醚基胺马来酸盐(SM1044)诱导活性氧产生促进SU-DHL-4细胞凋亡的机制。方法:流式细胞术检测SM1044对SU-DHL-4细胞活性氧的水平影响;流式细胞术检测SU-DHL-4细胞的凋亡情况及蛋白质印迹检测凋亡相关蛋白的表达;免疫荧光技术检测细胞内钙离子的荧光强度及蛋白质印迹检测内质网应激相关蛋白CCAAT/增强子结合蛋白(C/EBP)腺苷环磷酸反应元件结合转录因子同源蛋白(CHOP)的表达。结果:SM1044可诱导SU-DHL-4细胞产生活性氧,且具有时间依赖性(r=0.951,P=0.003);SM1044可诱导SU-DHL-4细胞凋亡及凋亡相关蛋白的活化,使用N-乙酰半胱氨酸(NAC)清除活性氧后,SM1044诱导SU-DHL-4细胞凋亡的作用被抑制(P<0.01),凋亡相关蛋白的表达也被抑制;SM1044可促进SU-DHL-4细胞内钙离子水平的升高以及内质网应激相关蛋白CHOP的表达,使用NAC清除活性氧后,钙离子水平的升高以及CHOP蛋白的表达被抑制。结论:SM1044可通过诱导SU-DHL-4细胞产生活性氧促进SU-DHL-4细胞凋亡,其机制可能与活性氧激活钙离子-内质网应激有关。
OBJECTIVE: To study the mechanism of artemisinin derivatives of artemether maleate (SM1044) inducing active oxygen production and promoting apoptosis of SU-DHL-4 cells. Methods: The effect of SM1044 on reactive oxygen species in SU-DHL-4 cells was detected by flow cytometry. The apoptosis of SU-DHL-4 cells was detected by flow cytometry and the expression of apoptosis-related protein was detected by Western blotting. The fluorescence intensity of intracellular Ca2 + was detected and Western blotting was used to detect the expression of endoplasmic reticulum stress related protein CCAAT / enhancer binding protein (C / EBP) adenosine monophosphate response element binding transcription factor homologous protein (CHOP). Results: SM1044 could induce the generation of reactive oxygen species in SU-DHL-4 cells in a time-dependent manner (r = 0.951, P = 0.003). SM1044 induced the apoptosis of SU-DHL-4 cells and the activation of apoptosis- After scavenging reactive oxygen species (NAC), the effect of SM1044 on the apoptosis of SU-DHL-4 cells was inhibited (P <0.01), and the expression of apoptosis-related proteins was also inhibited. SM1044 could promote SU- DHL-4 intracellular calcium levels and endoplasmic reticulum stress-related protein CHOP expression, NAC scavenging reactive oxygen species, the increase in calcium levels and CHOP protein expression was inhibited. CONCLUSIONS: SM1044 can promote the apoptosis of SU-DHL-4 cells by inducing the production of reactive oxygen species in SU-DHL-4 cells. The mechanism may be related to the activation of calcium and endoplasmic reticulum stress.