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作 者:侯著法[1] 赵冰洁[1] 刘松山[1] 易文静 车虹[1] HOU Zhu-Fa;ZHAO Bing-Jie;LIU Song-Shan;YI Wen-Jing;CHE Hong(Department of Hematology,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,Sichuan Province,China)
机构地区:[1]成都中医药大学附属医院血液科,四川成都610072
出 处:《中国实验血液学杂志》2023年第2期435-441,共7页Journal of Experimental Hematology
摘 要:目的:探讨对香豆酸对多发性骨髓瘤细胞凋亡的影响及相关作用机制。方法:选择多发性骨髓瘤细胞MM.1s,以不同浓度对香豆酸(0、0.4、0.8、1.6、3.2 mmol/L)作用于MM.1s细胞,采用CCK-8法检测细胞抑制率及半数抑制浓度(IC_(50));并以1/2 IC_(50)、IC_(50)、2 IC_(50)及转染ov-Nrf-2、ov-Nrf-2+IC_(50)作用于MM.1s细胞,采用流式细胞术检测细胞凋亡、ROS荧光强度及线粒体膜电位;采用蛋白质印迹法(Western blot)检测细胞Nrf-2、HO-1蛋白相对表达量。结果:对香豆酸以剂量依赖性方式抑制MM.1s细胞的增殖(r=0.997),其IC_(50)值为2.754 mmol/L;与对照组相比,1/2 IC_(50)组、IC_(50)组、2 IC_(50)组、ov-Nrf-2+IC_(50)组细胞凋亡及ROS荧光强度均明显增加(P<0.01),IC_(50)组、2 IC_(50)组Nrf-2、HO-1蛋白表达均明显降低(P<0.05);与IC_(50)组相比,ov-Nrf-2+IC_(50)组细胞凋亡、ROS荧光强度明显降低(P<0.01),Nrf-2、HO-1蛋白表达明显升高(P<0.01)。结论:对香豆酸能抑制MM.1s细胞增殖,可能靶向Nrf-2/HO-1信号通路影响MM细胞氧化应激从而诱导细胞凋亡。Objective:To investigate the effect of p-coumaric acid on apoptosis of multiple myeloma cells and its related mechanism.Methods:Multiple myeloma cell line MM.1s cells were selected and treated with different concentrations of p-coumaric acid(0,0.4,0.8,1.6,3.2 mmol/L),and the inhibition rate and half inhibition concentration(IC_(50))were detected by CCK-8 method.Then MM.1s cells were treated with 1/2 IC_(50),IC_(50),2 IC_(50) and transfected with ov-Nrf-2 and ov-Nrf-2+IC_(50).The apoptosis,ROS fluorescence intensity and mitochondrial membrane potential of MM.1s cells were detected by flow cytometry,and the relative expressions of cellular Nrf-2 and HO-1 protein were detected by Western blot.Results:P-coumaric acid inhibited the proliferation of MM.1s cells in a dosedependent manner(r=0.997)with an IC_(50) value of 2.754 mmol/L.Compared with the control group,apoptosis and ROS fluorescence intensity of MM.1s cells were significantly increased in the 1/2 IC_(50) group,IC_(50) group,2 IC_(50) group and ov-Nrf-2+IC_(50) group(P<0.01),the expressions of Nrf-2,HO-1 protein in the IC_(50) group and 2 IC_(50) group were significantly decreased(P<0.05).Compared with the IC_(50) group,the cells apoptosis and ROS fluorescence intensity were significantly decreased(P<0.01),and the expressions of Nrf-2 and HO-1 protein were significantly increased in the ov-Nrf-2+IC_(50) group(P<0.01).Conclusion:P-coumaric acid can inhibit the proliferation of MM.1s cells and may target the Nrf-2/HO-1 signaling pathway to affect oxidative stress in MM cells thereby inducing their apoptosis.
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