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Cancer Chemotherapy and Pharmacology

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01.04.2014 | Original Article

Simvastatin suppresses head and neck squamous cell carcinoma ex vivo and enhances the cytostatic effects of chemotherapeutics

verfasst von: Matthaeus Stoehr, Christian Mozet, Andreas Boehm, Achim Aigner, Andreas Dietz, Gunnar Wichmann

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2014

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Abstract

Purpose

Simvastatin (Sim) is approved as lipid-controlling drug in patients with cardiovascular risk to reduce hypercholesterolemia. Recent publications indicate possible inhibitory effects of Sim on tumor cell lines, and epidemiological data suggest activity in cancer patients. Still, its therapeutic efficacy, particularly in head and neck squamous cell carcinoma (HNSCC), remains to be elucidated. This study analyzes the effects of Sim on HNSCC cell lines (KB, HN5, FaDu) and on a larger set of primary HNSCC cells by employing a short-time ex vivo colony formation test (FLAVINO assay). Possible additive or synergistic effects of Sim combinations with established chemotherapeutics are determined as well.

Methods

Biopsies of 49 HNSCC were tested in the FLAVINO assay with Sim alone or in combination with cisplatin (Cis) or docetaxel (DTX). Cell lines were studied for reference. Epithelial HNSCC cells were stained by Cy2-labeled anti-cytokeratin antibodies facilitating the detection of colony formation (CF) by immunofluorescence. Drug combinations were analyzed regarding their interaction.

Results

Sim alone acted suppressive on tested cell lines and increased the cytostatic efficacy of Cis and DTX. 18/49 HNSCC qualified for FLAVINO-based dose-response analyses, and Sim significantly suppressed CF in 18/18 primary HNSCC. Moreover, Sim increased cytotoxic effects of Cis and DTX, primarily in an additive mode of action.

Conclusions

The ex vivo tumor cell inhibition of Sim and its additive effects upon combination with established cytostatics provide the basis for epidemiological and clinical studies on statins, potentially directed toward co-medication in future treatment regimens.

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Titel: Simvastatin suppresses head and neck squamous cell carcinoma ex vivo and enhances the cytostatic effects of chemotherapeutics
verfasst von: Matthaeus Stoehr
Christian Mozet
Andreas Boehm
Achim Aigner
Andreas Dietz
Gunnar Wichmann
Publikationsdatum: 01.04.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2412-1

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