ArticleJournal of experimental & clinical cancer research : CR2018
A novel small molecule inhibitor of MDM2-p53 (APG-115) enhances radiosensitivity of gastric adenocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- TWIST1 bridges p53 and MDM2 and impairs the efficacy of MDM2 inhibitors.Journal of experimental & clinical cancer research : CR · 2026Article
- MST4 plays dual roles in lung adenocarcinoma by regulating homeostasis of wild-type and mutant p53 protein.Oncogene · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Novel antagonist APG-115 targets MDM2-p53 to induce p53-mediated apoptosis and radiosensitization in colorectal cancer.Clinical and experimental medicine · 2026Article
- MDM2-P53-V-ATPases axis driven by dehydroevodiamine to fight intracellular bacterial infection.Communications biology · 2025Article
- MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets.BMC cancer · 2025Article
- APG-115 synergizes with bortezomib to induce apoptosis in cervical cancer cells.Anti-cancer drugs · 2025Article
- Synergistic effect of MDM2 inhibitors and radiotherapy in endometrial cancer.NPJ precision oncology · 2025Article
- p53 in colorectal cancer: from a master player to a privileged therapy target.Journal of translational medicine · 2025Review
- Review
- The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53-MDM2 Modulation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Exploring the anti-gastric cancer mechanisms of Diosgenin through integrated network analysis, bioinformatics, single-cell sequencing, and cell experiments.Frontiers in pharmacology · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- SNPs Give LACTB Oncogene-Like Functions and Prompt Tumor Progression via Dual-Regulating p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling.Journal of experimental & clinical cancer research : CR · 2024Article
- A first-in-human phase I study of a novel MDM2/p53 inhibitor alrizomadlin in advanced solid tumors.ESMO open · 2024Article
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Quercetin promotes ATG5-mediating autophagy-dependent ferroptosis in gastric cancer.Journal of molecular histology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGastric cancer is the leading cause of cancer related death worldwide. Radiation alone or combined with chemotherapy plays important role in locally advanced and metastatic gastric adenocarcinoma. MDM2-p53 interaction and downstream signaling affect cellular response to DNA damage which leads to cell cycle arrest and apoptosis. Therefore, restoring p53 function by inhibiting its interaction with MDM2 is a promising therapeutic strategy for cancer. APG-115 is a novel small molecule inhibitor which blocks the interaction of MDM2 and p53. In this study, we investigated that the radiosensitivity of APG-115 in gastric adenocarcinoma in vitro and in vivo.
methodsThe role of APG-115 in six gastric cancer cells viability in vitro was determined by CCK-8 assay. The expression level of MDM2, p21, PUMA and BAX in AGS and MKN45 cell lines was measured via real-time PCR (RT-PCR). The function of treatment groups on cell cycle and cell apoptosis were detected through Flow Cytometry assay. Clonogenic assays were used to measure the radiosensitivity of APG-115 in p53 wild type gastric cancer cell lines. Western blot was conducted to detect the protein expressions of mdm2-p53 signal pathway. Xenograft models in nude mice were established to explore the radiosensitivity role of APG-115 in gastric cancer cells in vivo.
resultsWe found that radiosensitization by APG-115 occurred in p53 wild-type gastric cancer cells. Increasing apoptosis and cell cycle arrest was observed after administration of APG-115 and radiation. Radiosensitivity of APG-115 was mainly dependent on MDM2-p53 signal pathway. In vivo, APG-115 combined with radiation decreased xenograft tumor growth much more significantly than either single treatment. Moreover, the number of proliferating cells (Ki-67) significantly decreased in combination group compared with single treatment group.
conclusionsIn summary, we found that combination of MDM2-p53 inhibitor (APG-115) and radiotherapy can enhance antitumor effect both in vitro and in vivo. This is the first report on radiosensitivity of APG-115 which shed light on clinical trial of the combination therapy of radiation with APG-115 in gastric adenocarcinoma.
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Registered trials
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