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

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。

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

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.