Artikel
Cytotoxic effect of statins and thiazolidinediones against glioblastoma multiforme
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Autoren
Veröffentlicht: | 20. Mai 2009 |
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Gliederung
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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.