title: Simvastatin suppresses head and neck squamous cell carcinoma ex vivo and enhances the cytostatic effects of chemotherapeutics.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany, matthaeus.stoehr@medizin.uni-leipzig.de.
authors.forename: Matthaeus
authors.initials: M
authors.lastname: Stoehr
authors.forename: Christian
authors.initials: C
authors.lastname: Mozet
authors.forename: Andreas
authors.initials: A
authors.lastname: Boehm
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
authors.forename: Andreas
authors.initials: A
authors.lastname: Dietz
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wichmann
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007624:KB Cells; D008297:Male; D009367:Neoplasm Staging; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D043823:Taxoids; D000077143:Docetaxel; D019821:Simvastatin; D002945:Cisplatin