Fluvastatin inhibits growth and alters the malignant phenotype of the C6 glioma cell line |
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| Institution: | 1. Department of Cell Biology, Maria Curie-Sklodowska University, Lublin, Poland;2. Department of Virology and Immunology, Maria Curie-Sklodowska University, Lublin, Poland;1. Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, University Health Network Toronto General Hospital, 200 Elizabeth Street, 11E-215B Toronto, ON M5G 2C4, Canada;2. IPATIMUP, Institute of Molecular Pathology and Immunology of Porto University, Rua Dr Roberto Frias S/N, 4200-465, Porto, Portugal;1. Nicholas School of the Environment, Duke University, 308 Research Drive, A354 Levine Science Research Center, Durham, NC 27708, USA;2. Toxicology Program, School of Public Health, Environmental Health Sciences Department, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA;3. Simulation Group, Samsung SDI, Suwon-si, Gyeonggi-do, Republic of Korea;4. H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA;1. Department of Cardio-Thoracic and Vascular Surgery, Örebro University Hospital and Örebro University, Örebro, Sweden;2. Department of Surgery, Örebro University Hospital and Örebro University, Örebro, Sweden;1. Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA;1. Department of Neurology, Odense University Hospital & Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;2. Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark;3. Danish Cancer Society Research Centre, Danish Cancer Society, Copenhagen, Denmark;4. Department of Oncology, Odense University Hospital & Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;5. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark |
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| Abstract: | BackgroundFluvastatin is a member of the family of HMG-CoA reductase inhibitors (statins) extensively used in medical practice. Increasing evidence suggests that fluvastatin may be implicated in suppression of cancer growth and development. The aim of the present study was to investigate the anti-cancer potential of fluvastatin in C6 rat malignant glioma cells.MethodsFirst, the effects of fluvastatin on cell viability (MTT assay), proliferation (BrdU assay), cell morphology, and cytoskeleton were examined. Subsequently, its effect on extracellular signal regulated kinase 1 and 2 (ERK1/2) and c-Jun N-terminal kinase 1 and 2 (JNK 1/2) expression was estimated by Western blot. Finally, the influence of fluvastatin on cell migration and production of MMP-9 and VEGF was determined using a wound-healing assay and ELISA test, respectively.ResultsThe results obtained showed that fluvastatin had a remarkable inhibitory and cytotoxic effect on tumor C6 cells (IC50 = 8.6 μM, 48 h), but did not inhibit the growth of normal neuronal cells. The concentrations from 1 to 10 μM induced marked morphologic alterations typical for apoptosis including shrinkage of cytoplasm, chromatin condensation, and nucleus breakdown.ConclusionThe inhibitory effects of fluvastatin on cell proliferation seemed to be associated with decreased p-ERK1/2 expression, upregulation of p-JNK1/2, and reduction in the MMP-9 and VEGF concentrations in culture media. The high anticancer (antiproliferative, proapoptotic, antiinvasive) activity of fluvastatin and lack of its toxicity against normal cells indicate a potential use of this statin in the treatment of malignant glioma. |
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| Keywords: | Glioma cells Fluvastatin VEGF MMP-9 MAPKs Actin cytoskeleton |
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