In our study, we found that feedback accumulation of MDM2 induced by MDM2 inhibitors is strongly impaired by the combination treatment with Remodelin, causing higher p53 expression in p53 wild-type GC cells, which can enhance the antitumor efficacy of MDM2 inhibitors in the treatment of GC harboring wild-type p53. This evidence concerns the gene TP53 and gastric cancer.