The murine double minute 2 (MDM2)-p53 interaction inhibitor APG-115 demonstrates therapeutic potential in advanced malignancies. However, its molecular mechanism, especially for programmed death ligand 1 (PD-L1) immunotherapy modulation, remains poorly understood in thyroid cancer (TC). Herein, we conducted a series of in vitro and in vivo studies to investigate the therapeutic effect of APG-115 and the underlying molecular mechanisms in TC. We performed Cell Counting Kit (CCK-8) and cell scratch assay to assess the effect of APG-115 on the biological behavior of TC cells. Meanwhile, we performed animal experiments to investigate the therapeutic effect of APG-115 on TC in vivo. TC patient-derived organoids were further used to evaluate the potential value for clinical application of APG-115. Our results showed that APG-115 exhibited beneficial therapeutic effects in TC both in vitro and in vivo. Mechanistically, APG-115 restored the p53 antitumor effects by blocking MDM2-p53 binding and upregulating the PD-L1 expression. APG-115 downregulated Solute Carrier Family 7 Member 11 (SLC7A11) expression, contributing to lipid peroxidation and affecting PD-L1 expression in TC. Our study expands the clinical application value of APG-115 in cancer treatment, especially by further exploring the complex interplay between APG-115, PD-L1 immunotherapy, and ferroptosis.<\/p>\n","protected":false},"excerpt":{"rendered":"
The murine double minute 2 (MDM2)-p53 interaction inhibitor APG-115 demonstrates therapeutic potential in advanced malignancies. However, its molecular mechanism, especially for programmed death ligand 1 (PD-L1) immunotherapy modulation, remains poorly understood in thyroid cancer (TC). Herein, we conducted a series of in vitro and in vivo studies to investigate the therapeutic effect of APG-115 and […]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":[{"type":"text","value":"Lei Liang","user_id":0},{"type":"text","value":"Zhulan Chen","user_id":0},{"type":"text","value":"Defeng Lei","user_id":0},{"type":"text","value":"Chunwei Mo","user_id":0},{"type":"text","value":"Deren Lan","user_id":0},{"type":"text","value":"Juanru Ke","user_id":0},{"type":"text","value":"Weiqi Wang","user_id":0},{"type":"text","value":"Zhuo Yang","user_id":0},{"type":"text","value":"Xin Guo","user_id":0},{"type":"user_nicename","value":"Dong Chen","user_id":"31661"},{"type":"text","value":"Yongsheng Zhao","user_id":0},{"type":"text","value":"Haibo 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