João Basso, Ana Miguel Matos, Saeid Ghavami, Ana Fortuna, Rui Vitorino, Carla Vitorino
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引用次数: 0
Abstract
Pitavastatin is commonly prescribed to treat hypercholesterolemia through the regulation of cholesterol biosynthesis. Interestingly, it has also demonstrated a great potential for treating brain tumors, although the detailed cytotoxic mechanism, particularly in glioblastoma, remains incompletely understood. This work explores the activity of pitavastatin in 2D and 3D glioblastoma models, in an attempt to provide a more representative and robust overview of its anticancer potential in glioblastoma. The results show that not only is pitavastatin 10-1000 times-fold more effective in reducing tumoral metabolic activity than temozolomide, but also demonstrate a synergistic activity with this alkylating drug. In addition, low micromolar concentrations of this statin strongly impair the growth and the invasion ability of multicellular tumor spheroids. The obtained qRT-PCR and proteomics data highlight the modulation of cell death via apoptosis (BAX/BCL2, CASP9) and autophagy (BECN1, BNIP3, BNIP3L and LC3B), as well as an epithelial to mesenchymal transition blockage (HTRA1, SERPINE1, WNT5A, ALDH3B1 and EPHA2) and remodeling of the extracellular matrix (VCAN, SERPINE1 and TGFBI). Overall, these results lay the foundation for further investigations on the potential combinatory clinical treatment with temozolomide.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.