1. Nutlin-3, the small-molecule inhibitor of MDM2, promotes senescence and radiosensitises laryngeal carcinoma cells harbouring wild-type p53
- Author
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Richard Eccles, A.K. Arya, Carlos P. Rubbi, Mark T. Boyd, Bryony H. Lloyd, Terry Jones, A. El-Fert, D R Sibson, John D. Fenwick, Timothy Devling, Nikolina Vlatkovic, and Mohammed A Aslam
- Subjects
p53 ,Senescence ,Radiation-Sensitizing Agents ,Cancer Research ,Tumor suppressor gene ,Cell Survival ,squamous cell carcinoma of the head and neck ,Radiation Tolerance ,Piperazines ,chemistry.chemical_compound ,MDM2 ,Carcinoma ,medicine ,Animals ,Laryngeal Neoplasms ,Cellular Senescence ,Cell Proliferation ,biology ,ionising radiation ,Imidazoles ,Wild type ,Nutlin-3 ,Proto-Oncogene Proteins c-mdm2 ,Nutlin ,Laryngeal Neoplasm ,Genes, p53 ,medicine.disease ,Oncology ,chemistry ,Carcinoma, Squamous Cell ,biology.protein ,Cancer research ,laryngeal cancer ,Mdm2 ,Translational Therapeutics ,Cell aging - Abstract
BACKGROUND: Primary radiotherapy (RT) is a mainstay of treatment for laryngeal squamous cell carcinoma (LSCC). Although the cure rates for early (T1) vocal cord tumours are high, RT proves ineffective in up to a third of T3 carcinomas. Moreover, RT is associated with debilitating early- and late-treatment-related toxicity, thus finding means to de-escalate therapy, while retaining/augmenting therapeutic effectiveness, is highly desirable. p53 is a key mediator of radiation responses; we therefore investigated whether Nutlin-3, a small-molecule inhibitor of MDM2 (mouse double minute 2; an essential negative regulator of p53), might radiosensitise LSCC cells. METHODS: We performed clonogenic assays to measure radiosensitivity in a panel of LSCC cell lines (for which we determined p53 mutational status) in the presence and absence of Nutlin-3. RESULTS: LSCC cells harbouring wild-type p53 were significantly radiosensitised by Nutlin-3 (P
- Published
- 2010
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