gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

Cytotoxic effect of statins and thiazolidinediones against glioblastoma multiforme

Meeting Abstract

  • J. Tapia-Pérez - Klinik für Neurochirurgie, Klinikum der Otto von Guericke-Universität, Magdeburg
  • E. Kirches - Institut für Neuropathologie, Klinikum der Otto von Guericke-Universität, Magdeburg
  • C. Mawrin - Institut für Neuropathologie, Klinikum der Otto von Guericke-Universität, Magdeburg
  • R. Firsching - Klinik für Neurochirurgie, Klinikum der Otto von Guericke-Universität, Magdeburg
  • T. Schneider - Klinik für Neurochirurgie, Klinikum der Otto von Guericke-Universität, Magdeburg

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP14-04

DOI: 10.3205/09dgnc402, URN: urn:nbn:de:0183-09dgnc4024

Published: May 20, 2009

© 2009 Tapia-Pérez et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Statins are inhibitors of the cholesterol pathway with several pleiotropic effects. The different statins show important intermolecular differences. Thiazolidinediones (TDZ) are Peroxisomal Proliferator Activator Receptor (PPAR) gamma agonists with a potent anti-inflammatory pro-apoptotic activity. For both kinds of drugs a dose-dependent effect against glioblastoma multiforme seems to exist and the combination could enhance this effect. Up to now a direct comparison of several statins and TDZ has not been performed, which is, however, necessary before planning a chemotherapeutic proposal.

Methods: We compared the anti-glioma effect of simvastatin (SMV), atorvastatin (ATV), lovastatin (LVS), pravastatin (PVS), rosiglitazone (RGZ), pioglitazone (PGZ), and their combinations at several concentrations using human glioblastoma cell lines U87, U 138, LN 405 and rat cell line RG II. The response was assessed using a cell proliferation assay, and the results were reported as percent of cell death in comparison to untreated control cells after 48 and 144 hours.

Results: After 48 hours LVS at 5μM (>50% cell death) and the combination ATVS 1.5μM /PGZ 40μM (>60%) were the most effective drugs. After 144 hours LVS 5μM (>85%) and the combination ATVS 1.5μM /PGZ 40μM (>90%) presented the highest cytotoxic effect. PVS and its combinations with TDZ showed the weakest effect (max. 49%). PGZ combined with a statin was more potent than RGZ and a statin.

Conclusions: The combination of statins, especially ATV, and thiazolidinediones, preferably PGZ, shows a remarkable cytotoxic effect against human glioblastoma cells. In vivo trials should be continued because of these promising in vitro results.