ArticleMolecular cancer2014
Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- Integrative analysis of multi-omics data identified PLG as key gene related to Anoikis resistance and immune phenotypes in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.Journal of hepatocellular carcinoma · 2024Review
- Nutlin-3 suppresses tumorigenesis and progression of oral squamous cell carcinoma and enhances chemosensitivity to cisplatin.Cytotechnology · 2023Article
- TRIM proteins in hepatocellular carcinoma.Journal of biomedical science · 2022Review
- Albumin-Embellished Arsenic Trioxide-Loaded Polymeric Nanoparticles Enhance Tumor Accumulation and Anticancer Efficacy via Transcytosis for Hepatocellular Carcinoma Therapy.AAPS PharmSciTech · 2022Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Comprehensive Analysis to Identify the Epithelial-Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma.Frontiers in surgery · 2021Article
- Review
- Trisenox Disrupts MDM2-DAXX-HAUSP Complex and Induces Apoptosis in a Mouse Model of Acute Leukemia.Journal of Cancer · 2020Article
- Super-enhancer-driven AJUBA is activated by TCF4 and involved in epithelial-mesenchymal transition in the progression of Hepatocellular Carcinoma.Theranostics · 2020Article
- Arsenic Trioxide Inhibits the Metastasis of Small Cell Lung Cancer by Blocking Calcineurin-Nuclear Factor of Activated T Cells (NFAT) Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- MDM2-p53 Interactions in Human Hepatocellular Carcinoma: What Is the Role of Nutlins and New Therapeutic Options?Journal of clinical medicine · 2018Review
- Synergistic effect of nutlin-3 combined with aspirin in hepatocellular carcinoma HepG2 cells through activation of Bcl-2/Bax signaling pathway.Molecular medicine reports · 2018Article
- Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology.Frontiers in pharmacology · 2018Article
- Article
- Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis.Experimental & molecular medicine · 2017Article
- Low-dose Actinomycin-D treatment re-establishes the tumoursuppressive function of P53 in RELA-positive ependymoma.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundArsenic trioxide has been demonstrated as an effective anti-cancer drug against leukemia and solid tumors both in vitro and in vivo. However, recent phase II trials demonstrated that single agent arsenic trioxide was poorly effective against hepatocellular carcinoma (HCC), which might be due to drug resistance.
methodsMutation detection of p53 gene in arsenic trioxide resistant HCC cell lines was performed. The therapeutic effects of arsenic trioxide and Nutlin-3 on HCC were evaluated both in vitro and in vivo. A series of experiments including MTT, apoptosis assays, co-Immunoprecipitation, siRNA transfection, lentiviral infection, cell migration, invasion, and epithelial-mesenchy-mal transition (EMT) assays were performed to investigate the underlying mechanisms.
resultsThe acquisition of p53 mutation contributed to arsenic trioxide resistance and enhanced metastatic potential of HCC cells. Mutant p53 (Mutp53) silence could re-sensitize HCC resistant cells to arsenic trioxide and inhibit the metastatic activities, while mutp53 overexpression showed the opposite effects. Neither arsenic trioxide nor Nutlin-3 could exhibit obvious effects against arsenic trioxide resistant HCC cells, while combination of them showed significant effects. Nutlin-3 can not only increase the intracellular arsenicals through inhibition of p-gp but also promote the p73 activation and mutp53 degradation mediated by arsenic trioxide. In vivo experiments indicated that Nutlin-3 can potentiate the antitumor activities of arsenic trioxide in an orthotopic hepatic tumor model and inhibit the metastasis to lung.
conclusionsAcquisitions of p53 mutations contributed to the resistance of HCC to arsenic trioxide. Nutlin-3 could overcome arsenic trioxide resistance and inhibit tumor metastasis through p73 activation and promoting mutant p53 degradation mediated by arsenic trioxide.
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