ArticleOncotarget2015
The MDM2-inhibitor Nutlin-3 synergizes with cisplatin to induce p53 dependent tumor cell apoptosis in non-small cell lung cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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The trial behind it
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Who cites it
43 citing papers in PubMed, 73 citations in OpenAlex.
- ITGB4 up-regulated by STAT3 reduces the sensitivity of bladder cancer to cisplatin by suppressing p53.British journal of cancer · 2026Article
- Role of the "inflammation-immunity-metabolism" network in non-small cell lung cancer: a multi-omics analysis.Discover oncology · 2025Article
- Enzymatic Desymmetrisation of ProchiralMolecules (Basel, Switzerland) · 2024Article
- MDM2/MDMX inhibition by Sulanemadlin synergizes with anti-Programmed Death 1 immunotherapy in wild-type p53 tumors.iScience · 2024Article
- Pulmonary immune response regulation, genotoxicity, and metabolic reprogramming by menthol- and tobacco-flavored e-cigarette exposures in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Induction of synergistic apoptosis by tetramethoxystilbene and nutlin-3a in human cervical cancer cells.Toxicological research · 2022Article
- Repressed miR-34a Expression Dictates the Cell Fate to Corneal Endothelium Failure.Investigative ophthalmology & visual science · 2022Article
- Review
- CircTP53 promotes the proliferation of thyroid cancer via targeting miR-1233-3p/MDM2 axis.Journal of endocrinological investigation · 2021Article
- Genome-scale CRISPR screening identifies cell cycle and protein ubiquitination processes as druggable targets for erlotinib-resistant lung cancer.Molecular oncology · 2021Article
- Characterization of acquired nutlin-3 resistant non-small cell lung cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Sempervirine inhibits RNA polymerase I transcription independently from p53 in tumor cells.Cell death discovery · 2020Article
- MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling.Genes & development · 2020Article
- Cisplatin in Combination with MDM2 Inhibition Downregulates Rad51 Recombinase in a Bimodal Manner to Inhibit Homologous Recombination and Augment Tumor Cell Kill.Molecular pharmacology · 2020Article
- LncRNA FOXD3-AS1 promoted chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis.Cancer cell international · 2020Article
- Radiosensitization of Non-Small Cell Lung Cancer Cells by the Plk1 Inhibitor Volasertib Is Dependent on the p53 Status.Cancers · 2019Article
- Hypoxia‑induced internalization of connexin 26 and connexin 43 in pulmonary epithelial cells is involved in the occurrence of non‑small cell lung cancer via the P53/MDM2 signaling pathway.International journal of oncology · 2019Article
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- Article
- ZCCHC10 suppresses lung cancer progression and cisplatin resistance by attenuating MDM2-mediated p53 ubiquitination and degradation.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53/MDM2 interaction has been a well-studied target for new drug design leading to the development of the small molecule inhibitor Nutlin-3. Our objectives were to combine Nutlin-3 with cisplatin (CDDP), a well-known activator of the p53 pathway, in a series of non-small cell lung cancer cell lines in order to increase the cytotoxic response to CDDP. We report that sequential treatment (CDDP followed by Nutlin-3), but not simultaneous treatment, resulted in strong synergism. Combination treatment induced p53's transcriptional activity, resulting in increased mRNA and protein levels of MDM2, p21, PUMA and BAX. In addition we report the induction of a strong p53 dependent apoptotic response and induction of G2/M cell cycle arrest. The strongest synergistic effect was observed at low doses of both CDDP and Nutlin-3, which could result in fewer (off-target) side effects while maintaining a strong cytotoxic effect. Our results indicate a promising preclinical potential, emphasizing the importance of the applied treatment scheme and the presence of wild type p53 for the combination of CDDP and Nutlin-3.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.