Nultin-3联合顺铂对口腔鳞状细胞癌细胞的抑制作用及机制研究  

Inhibitory effect and mechanism of Nultin-3 combined with cisplatin on oral squamous cell carcinoma

作　　者：施俊[1] 倪小兵[1] 毛敏[1] 彭兴春 SHI Jun;NI Xiaobing;MAO Min;PENG Xingchun(Department of Stomatology,Taihe Hospital,Hubei University of Medicine,Shiyan 442000,China;School of Basic Medical Sciences,Hubei University of Medicine)

机构地区：[1]湖北医药学院附属太和医院口腔科,十堰442000 [2]湖北医药学院基础医学院

出　　处：《实用肿瘤学杂志》2018年第6期488-492,共5页Practical Oncology Journal

基　　金：湖北省教育厅科研计划项目(编号:B2018109);湖北医药学院2017年教学研究项目(编号:2017035; 2017032)

摘　　要：目的探讨MDM2抑制剂Nultin-3联合顺铂对口腔鳞状细胞癌Tca8113细胞的抑制作用及其机制。方法将人口腔鳞状细胞癌Tca8113细胞分为对照组、顺铂组、Nultin-3组及Nultin-3联合顺铂组(联合组),采用噻唑蓝(MTT)法分别检测各组Tca8113细胞处理48 h后的增殖率;采用蛋白质印迹法检测各组细胞MDM2、p53及凋亡相关蛋白Caspase-3和Caspase-9的表达。结果联合组处理后口腔鳞状细胞癌Tca8133细胞的增殖率明显低于其它各组,差异具有统计学意义(P <0. 05)。联合组Caspase-9、Caspase-3及p53蛋白的相对表达量明显高于顺铂组和Nultin-3组(P <0. 05);此外,联合组MDM2蛋白的相对表达量显著低于顺铂组和Nultin-3组(P <0. 05)。结论 Nultin-3联合顺铂作用于口腔鳞癌细胞Tca8113时具有协同增效作用。Nultin-3通过调控MDM2-p53信号通路并上调促凋亡蛋白Caspase-9及Caspase-3的表达水平,以达到增强顺铂抑制口腔鳞状细胞癌的作用,从而为相关临床研究及治疗提供坚实的理论基础。Objective The objective of this study was to investigate the inhibitory effect of MDM2 inhibitor Nultin-3 combined with cisplatin on human oral squamous cell carcinoma(OSCC)Tca8113 cells and its mechanism.Methods Human OSCC Tca8113 cells were treated with Nultin-3,cisplatin,Nultin-3 combined with cisplatin,or vehicle control groups.The proliferation of Tca8113 cells was determined by thiazolyl blue(MTT)assay.The expression of MDM2,P53,Caspase-9 and Caspase-3 protein was determined by Western blot.Results The proliferative rate of OSCC ca8133 cells treated with Nultin-3 combined with cisplatin was significantly lower than that of other groups(P<0.05).The relative expression of Caspase-9,Caspase-3 and P53 protein in the Nultin-3 combined with cisplatin was significantly higher than those of the Nultin-3 and cisplatin alone groups(P<0.05).In addition,the relative expression of MDM2 protein in the Nultin-3 combined with cisplatin group was significantly lower than that of the cisplatin and Nultin-3 alone groups(P<0.05).Conclusion Nultin-3 combined with cisplatin has synergistic effect on oral squamous cell carcinoma Tca8113 cells.Nultin-3 regulates the MDM2-p53 signaling pathway and up-regulates the expression of proapoptotic proteins Caspase-9 and Casapase-3 to enhance the inhibition of cisplatin on oral squamous cell carcinoma,providing a solid theoretical basis for clinical research and treatment.

关 键 词：Nultin-3 顺铂 TCA8113细胞 MDM2 p53 

分 类 号：R782.05[医药卫生—口腔医学]