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The effect of Nutlin‐3 on laryngeal carcinoma cell lines with wild‐type p53: a promising treatment strategy for laryngeal carcinoma
Author(s) -
Arya A.K.,
ElFert A.,
Devlin T.,
Jones T.M.,
Boyd M.T.
Publication year - 2008
Publication title -
clinical otolaryngology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.914
H-Index - 68
eISSN - 1749-4486
pISSN - 1749-4478
DOI - 10.1111/j.1749-4486.2008.01747_2.x
Subject(s) - flow cytometry , cell culture , apoptosis , cancer research , medicine , carcinoma , cell , mdm2 , cell cycle , wild type , cancer , mutant , biology , immunology , gene , genetics
Objectives. Abnormalities of the p53 gene are the commonest mutation found in all human cancers, and evidence suggests this may influence response to chemoradiotherapeutic agents. Nutlin‐3, the small molecule inhibitor of MDM2/p53 interaction, has been shown to be effective in prostate cancer and leukemia by inducing apoptosis in cells with functioning p53. It is this effect that we wished to demonstrate in laryngeal carcinoma. Methods. Eight cell lines derived from patients with laryngeal carcinoma were used in this study. Other cell lines from other sites of the head and neck were deliberately excluded to avoid using heterogeneous cell types. The p53 status of the cell lines was determined using direct sequence analysis of the entire coding length of the gene (exons 2–11). Cell lines were treated with Nutlin‐3 for 48 h and surviving cells were counted using the Beckman Coulter Counter. Flow cytometry was used to determine cell cycle characteristics. Results. Four cell lines harboured p53 mutations, four contained wild‐type p53. All cell lines with wild type p53 were sensitive to the effects of Nutlin‐3 in a time and dose dependant manner. Cell lines harbouring mutant p53 were resistant to Nutlin‐3. Flow cytometry demonstrated an increase in p53‐dependant apoptosis in responsive cell lines. Conclusions. This is the first study to demonstrate that Nutlin‐3 is effective in laryngeal cancer cell lines with wild‐type p53. The clinical application of Nutlin‐3 could provide a new and targeted treatment option for patients with laryngeal carcinoma.