顺铂通过ROS介导ClC-3上调诱导鼻咽癌细胞凋亡  

Cisplatin induces apoptosis in nasopharyngeal carcinoma cells by up-reg⁃ulates of the expressions of ClC-3 via ROS mediation

作　　者：徐培声 林嘉伟 俞美声 谭秋婵 朱林燕[3] 彭爽[4] 陈丽新[3] 王亮[5] 王立伟[1] XU Pei-sheng;LIN Jia-wei;YU Mei-sheng;TAN Qiu-chan;ZHU Lin-yan;PENG Shuang;CHEN Li-xin;WANG Liang;WANG Li-wei(Department of Physiology,School of Medicine,Jinan University,Guangzhou 510632,China;The First People's Hospital of Foshan,Foshan 528000,China;Department of Pharmacology,School of Medicine,Jinan University,Guangzhou 510632,China;Department of Pathophysiology,School of Medicine,Jinan University,Guangzhou 510632,China;Department of Oncology,The First Affiliated Hospital,Jinan University,Guangzhou 510632,China;Department of Physiology,Guang-zhou Health Science College,Guangzhou 510180,China)

机构地区：[1]暨南大学基础与公共卫生学院生理学系,广东广州510632 [2]佛山市第一人民医院,广东佛山528000 [3]暨南大学基础与公共卫生学院药理学系,广东广州510632 [4]暨南大学基础与公共卫生学院病理生理学系,广东广州510632 [5]暨南大学第一附属医院肿瘤科,广东广州510632 [6]广州卫生职业技术学院生理学系,广东广州510180

出　　处：《中国病理生理杂志》2021年第6期1091-1098,共8页Chinese Journal of Pathophysiology

基　　金：广东省科技计划项目(No.2017A050501021);广州市教育局高校科研项目(No.202032841)。

摘　　要：目的:探讨ClC-3氯通道在顺铂诱导的鼻咽癌细胞凋亡中的作用及机制。方法:将不同浓度的顺铂作用于人低分化鼻咽癌细胞(CNE-2Z细胞);MTT法检测不同浓度的顺铂处理24 h和48 h后细胞活力;采用ClC-3-siRNA下调ClC-3的表达,Annexin V-FITC/PI双染法检测细胞凋亡,多功能微孔板检测仪和流式细胞术检测细胞不同状态下的ROS水平。结果:(1)顺铂呈时间和浓度依赖性抑制CNE-2Z细胞生长,氯通道阻断剂DIDS显著抑制顺铂引起的细胞凋亡(P<0.01);(2)顺铂促进CNE-2Z细胞ClC-3表达,下调ClC-3蛋白表达后,顺铂诱导的细胞凋亡率下降(P<0.05);(3)顺铂促进CNE-2Z细胞ROS产生,用抗氧化剂抑制细胞产生ROS后,顺铂诱导的ClC-3蛋白表达和凋亡被抑制,而下调ClC-3蛋白表达对ROS水平影响不大。结论:顺铂可通过提升CNE-2Z细胞ROS水平,上调氯通道ClC-3蛋白水平,从而诱导细胞凋亡。AIM:To study the role of ClC-3 chloride channel in cisplatin-induced apoptosis of nasopharyngeal carcinoma cells and the underlying mechanism.METHODS:Different concentrations of cisplatin were used to induce apoptosis in human poorly differentiated nasopharyngeal carcinoma CNE-2Z cells.The viability of the cells treated with cis‐platin for 24 h and 48 h was measured by MTT assay.ClC-3 gene was silenced by ClC-3 small interfering RNA(siRNA)in CNE-2Z cells.The apoptosis rate was analyzed by flow cytometry with Annexin V-FITC/PI staining.Multifunction micro‐plate detector and flow cytometry were used to detect reactive oxygen species(ROS)levels.RESULTS:Cisplatin inhibited the growth of CNE-2Z cells in a time and concentration dependent manners,chloride channel blocker DIDS de‐pressed cisplatin-induced apoptosis(P<0.01).Cisplatin promoted the expression of ClC-3 in CNE-2Z cells.Cisplatin-in‐duced apoptotic rate was decreased by down-regulation of ClC-3 protein expression(P<0.05).Cisplatin increased ROS production in CNE-2Z cells.After inhibiting ROS production by L-NAC,cisplatin-induced up-regulation of ClC-3 protein expression and apoptosis were inhibited,while down-regulation of ClC-3 had little effect on ROS level.CONCLUSION:Cisplatin induces apoptosis in CNE-2Z cells by up-regulating the expressions of ClC-3 via ROS mediation.

关 键 词：鼻咽癌 ClC-3通道 顺铂 活性氧簇 细胞凋亡 

分 类 号：R739.6[医药卫生—肿瘤] R730.23[医药卫生—临床医学]