二甲基塞来昔布通过活性氧诱导乳腺癌细胞凋亡  

Dimethyl celecoxib induces apoptosis of breast cancer cells by reactive oxygen species

作　　者：雷小梅 侯春燕[1] 闫雪梅 段丽丽[1] 王映芬 谭潭[1,2] LEI Xiaomei;HOU Chunyan;YAN Xuemei;DUAN Lili;WANG Yingfen;TAN Tan(Chenzhou First People's Hospital,Hunan Chenzhou 423000,China;The First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China)

机构地区：[1]郴州市第一人民医院,湖南郴州423000 [2]西安交通大学第一附属医院,陕西西安710061

出　　处：《现代肿瘤医学》2022年第22期4063-4067,共5页Journal of Modern Oncology

基　　金：湖南省科技计划项目(编号:2017SK51102,2017SK1103);湖南省卫生计生委科研项目(编号:20200861);陕西省肿瘤精准医学重点实验室开放课题(编号:KLTPM-SX2018-B5);郴州市第一人民医院院内项目(编号:N2019-012,2021A001)。

摘　　要：目的:探讨二甲基塞来昔布(2,5-dimethyl celecoxib,DMC)对乳腺癌细胞凋亡的作用。方法:用DMC处理人乳腺癌BT-20和MCF-7细胞,检测细胞生存率、细胞凋亡情况、细胞内ROS的产生;Caspase凋亡通路相关蛋白表达水平;预处理ROS抑制剂NAC、Caspase通路抑制剂Z-VAD-Fmk,检测细胞内Caspase凋亡通路蛋白表达水平。结果:DMC对BT-20和MCF-7细胞呈现浓度及时间依赖性杀伤作用,并可以明显增加细胞的凋亡,且呈现浓度依赖性趋势;DMC可以显著增加BT-20和MCF-7细胞内ROS的产生和凋亡相关蛋白cleaved caspase-7、9的表达水平;另一组实验证明,预处理NAC和Z-VAD-Fmk,可以明显降低cleaved caspase-7、9的表达水平,且抑制剂NAC组的效果大于Z-VAD-Fmk组。结论:DMC通过ROS途径诱导乳腺癌细胞发生凋亡。Objective:To investigate the effect of dimethyl celecoxib(DMC)on the apoptosis of breast cancer cells.Methods:Human breast cancer BT-20 and MCF-7 cells were treated with DMC to detect the survival rate,apoptosis and intracellular ROS production,Caspase apoptosis pathway related protein expression level.After pretreatment with ROS inhibitor NAC,Caspase pathway inhibitor Z-VAD-Fmk,the protein expression level of Caspase apoptosis pathway in cells was detected.Results:DMC showed concentration and time dependent killing effect on BT-20 and MCF-7 cells,and significantly increased cell apoptosis in a concentration dependent trend.DMC significantly increased ROS production and apoptosis related protein cleaved caspase-7/9 expression levels in BT-20 and MCF-7 cells.Another set of experiments demonstrated that pretreatment of NAC and Z-VAD-Fmk could significantly reduce cleaved caspase-7/9 expression levels,and the effect of inhibitor NAC group was greater than that of Z-VAD-Fmk group.Conclusion:DMC induces apoptosis of breast cancer cells through ROS pathway.

关 键 词：2 5-二甲基塞来昔布 活性氧 凋亡 

分 类 号：R737.31[医药卫生—肿瘤]