MDM2 inhibitor RG7388 potently inhibits tumors by activating p53 pathway in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a high-risk head and neck cancer with poor clinical outcomes and insufficient treatments. The mouse double minute 2 homolog (MDM2) is the main molecular target in the clinical treatment of cancer. Indeed, MDM2 negatively regulates p53 through ubiquitin-dependent degradation. Thus, inhibition of MDM2-p53 interaction is a potential strategy for treating NPC. The latest generation MDM2 inhibitor, RG7388, shows increased potency and improved bioavailability compared to previous treatments. In this study, we investigated the efficacy and specificity of this inhibitor in NPC cell lines, and tumor-bearing mice were used to examine the therapeutic efficacy and effects of RG7388 treatment. The results showed that RG7388 potently decreased cell proliferation and activated p53-dependent pathway, resulting in cell cycle arrest and apoptosis. RG7388 significantly inhibited tumors in tumor-bearing mice. Activation of the p53 pathway-inhibited cell proliferation, as observed by detecting Ki67-positive cells. Additionally, the activity of apoptotic caspase family proteins was induced in the cleaved caspase-3-positive cells in vivo. Our results demonstrate that the MDM2 small-molecule inhibitor RG7388 is effective for NPC tumors, supporting further clinical investigation as a potential therapy for NPC.