Abstract: 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.

Key words: Nultin-3, Cisplatin, Tca8113 cells, MDM2, P53