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

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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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Acknowledgments

The authors would like to thank the colleagues from the Institute of Pathology (C. Wittekind, J. Bertolini and U. Bauer) for providing histopathological data. The laboratory staff (A. Reiche, G. Müller and K. Herrmann) is acknowledged for technical assistance and in particular for material transfer from surgery and for handling of specimens. M. Stoehr and C. Mozet contributed equally to this study under the supervision of G. Wichmann.

Conflict of interest

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany

    Matthaeus Stoehr, Christian Mozet, Andreas Boehm, Andreas Dietz & Gunnar Wichmann

  2. Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Härtelstraße 16-18, 04107, Leipzig, Germany

    Achim Aigner

Authors
  1. Matthaeus Stoehr
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  2. Christian Mozet
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  3. Andreas Boehm
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  4. Achim Aigner
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  5. Andreas Dietz
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  6. Gunnar Wichmann
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Corresponding author

Correspondence to Matthaeus Stoehr.

Additional information

Matthaeus Stoehr and Christian Mozet have contributed equally to this work (shared first authorship).

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Stoehr, M., Mozet, C., Boehm, A. et al. Simvastatin suppresses head and neck squamous cell carcinoma ex vivo and enhances the cytostatic effects of chemotherapeutics. Cancer Chemother Pharmacol 73, 827–837 (2014). https://doi.org/10.1007/s00280-014-2412-1

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  • DOI: https://doi.org/10.1007/s00280-014-2412-1

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