摘要
目的探讨血小板衍生生长因子受体(platelet derived growth factor receptor,PDGFR)抑制剂CP 868596对A549细胞毒性的影响及其作用机制。方法MTT、流式细胞术及Caspase Glo 3/7检测CP 868596对细胞增殖及凋亡的影响。过氧化氢检测试剂盒检测CP 868596对细胞中ROS水平的影响。用Western blotting、qRT PCR及ARE测定Nrf2的表达。Western blotting测定P Akt的表达。结果CP 969586可抑制A549细胞增殖,并可诱导其细胞凋亡。在药物作用下,A549细胞内ROS水平显著升高,在给予NAC后,CP 868596诱导的细胞凋亡减少。CP 868596可抑制A549细胞中Nrf2蛋白的表达,并减少其mRNA水平。CP 868596也可抑制A549细胞中磷酸化Akt的表达水平。结论CP 868596可通过抑制A549细胞中Nrf2的表达,使得抗氧化信号受阻,进而导致ROS在A549细胞中大量累积,最终导致细胞凋亡。
Objective To investigate the effect of PDGFR inhibitor CP 868596 on the toxicity of A549 cells and its mechanism.Methods MTT,flow cytometry and Caspase Glo 3/7 were used to detect the effect of CP 868596 on cell proliferation and apoptosis.The hydrogen peroxide detection kit was used to detect the level of ROS in the cells of CP 868596.The expression of Nrf2 was determined by Western blotting and qRT PCR.The expression of p Akt was determined by Western blotting.Results CP 969586 inhibited the proliferation of A549 cells and induced apoptosis.Under the action of drugs,ROS levels in A549 cells were significantly increased,and NAC administration blocked apoptosis induced by CP 868596.CP 868596 inhibited the expression of Nrf2 protein in A549 cells and reduced its mRNA levels.CP 868596 also inhibited the expression of p Akt in A549 cells.Conclusion CP 868596 can inhibit the expression of Nrf2 in A549 cells,which block the anti oxidant sig naling pathway and accumulate cellular ROS,resulted in apoptosis.
作者
刘冰
杨智承
袁芳
LIU Bing;YANG Zhicheng;YUAN Fang(Guangdong Pharmaceutical University,Guangzhou 510006,China)
出处
《实用医学杂志》
CAS
北大核心
2019年第20期3124-3128,共5页
The Journal of Practical Medicine
基金
国家自然科学基金项目(编号：81472205)
