赖氨酸去甲基化酶5C抑制剂CPI-455对ESCC细胞系Eca-109增殖、凋亡的影响及其机制探讨  

The effect of lysine demethylase 5C inhibitor CPI-455 on proliferation and apoptosis in esophageal squamous cell carcinoma cell line Eca-109 and its mechanism

作　　者：薛晓婕[1,2] 刘彬 李文霞 XUE Xiaojie;LIU Bin;LI Wenxia(Department of Clinical Laboratory,Huangshi Central Hospital,Affiliated Hospital of Hubei Polytechnic University,Edong Healthcare Group,Hubei Huangshi 435000,China;Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention,Hubei Huangshi 435000,China;Huangshi Central Hospital,Affiliated Hospital of Hubei Polytechnic University,Edong Healthcare Group,Hubei Huangshi 435000,China.)

机构地区：[1]鄂东医疗集团黄石市中心医院(湖北理工学院附属医院)检验科,湖北黄石435000 [2]肾脏疾病发生与干预湖北省重点实验室,湖北黄石435000 [3]鄂东医疗集团黄石市中心医院(湖北理工学院附属医院),湖北黄石435000

出　　处：《现代肿瘤医学》2021年第13期2234-2238,共5页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:81773018);湖北省卫生健康科研基金(编号:WJ2019H449);湖北省医学青年拔尖人才计划。

摘　　要：目的:本研究探讨赖氨酸去甲基化酶5C(lysine demethylase 5C,KDM5C)抑制剂CPI-455对食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)细胞系Eca-109增殖、凋亡的影响及其机制。方法:运用MTT法、平板克隆形成实验检测CPI-455对Eca-109细胞增殖的抑制作用;透射电镜观察CPI-455对Eca-109细胞线粒体内部超微结构的影响;流式细胞仪检测CPI-455诱导Eca-109细胞中活性氧(reactive oxygen species,ROS)水平;Western blot测定CPI-455对Eca-109细胞中p53、Bax、KDM5C、Cleaved Caspase-9和Cleaved Caspase-3蛋白表达水平的影响。结果:MTT法、平板克隆形成实验结果分析显示:CPI-455能够抑制Eca-109细胞的增殖,具有时间、浓度依赖性,差异有统计学意义(P均<0.01);电镜下观察Eca-109细胞内结构显示:CPI-455引起Eca-109细胞中的线粒体固缩,线粒体缩小,结构紧密;流式细胞术和Western blot显示:CPI-455可以上调Eca-109细胞中ROS含量、p53、Bax、Cleaved Caspase-9和Cleaved Caspase-3的蛋白表达,同时下调KDM5C蛋白表达(P<0.05)。结论:CPI-455具有抑制Eca-109细胞增殖并诱导细胞凋亡的作用,其作用机制可能与下调KDM5C蛋白的表达有关。Objective:To investigate the effect of lysine demethylase 5C inhibitor CPI-455 in esophageal squamous cells carcinoma(ESCC)Eca-109 cells of proliferation and apoptosis as well as its mechanism.Methods:MTT assay and plate colone formation assay were used to detect the inhibitory effect of CPI-455 on the proliferation of Eca-109 cells.Transmission electron microscopy was used to observe ultrastructural changes of esophageal cancer Eca-109 cell induced by CPI-455.Flow cytometry was used to detect the level of ROS in Eca-109 cells induced by CPI-455.The expressions of p53,Bax,KDM5C,Cleaved Caspase-9 and Cleaved Caspase-3 were detected by Western blot.Results:Analysis of the results of the MTT assay and plate clone formation assay showed that CPI-55 inhibited the proliferation of Eca-109 cells in a time and concentration dependent manner,the difference were statistical significance(P<0.01).The structure of Eca-109 cells under transmission electron microscopy showed that CPI-455 induced pyknosis of mitochondria in Eca-109 cells,reduced mitochondria and compacted structure.Flow cytometry and Western blot showed that CPI-455 can up-regulated the expression levels of ROS,p53,Bax,Cleaved Caspase-9 and Cleaved Caspase-3 in Eca-109 cells.The expression level of KDM5C were down-regulated(P<0.05).Conclusion:CPI-455 can inhibit the proliferation of ECA-109 cells and induce apoptosis,which may be related to down-regulation of KDM5C expression.

关 键 词：KDM5C CPI-455 食管鳞状细胞癌 凋亡 CASPASE 

分 类 号：R735.1[医药卫生—肿瘤]