The PPARγ agonist pioglitazone crosses the blood-brain barrier and reduces tumor growth in a human xenograft model.
Cancer Chemother Pharmacol
; 71(4): 929-36, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23358645
ABSTRACT
PURPOSE:
The peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor family, represents a target in glioma therapy due to its antineoplastic effects in vitro on human glioma cell lines. We investigate the antineoplastic effects of the PPARγ agonist pioglitazone (pio) in a human glioma xenograft model to define the minimal required dose to induce antineoplastic effects. Additionally, we assess the ability of pio to cross the blood-brain barrier by measuring brain parenchymal concentration after oral administration.METHODS:
Human LN-229 cells were injected into the striatum of Balb/cJHanHsd-Prkdc-scid mice. Tumor volumes, invasion, proliferation and parenchymal pio concentrations were measured in this xenograft model after continuous intracerebral drug administration through an osmotic pump or after oral administration.RESULTS:
Continuous intracerebral or oral administration of pio reduced tumor volumes, invasion, and proliferation in vivo. To achieve a significant antineoplastic effect, pio needed to be dosed at 240 PPM in the oral group and >1 µM when delivered intracerebrally. After oral pio administration, the drug reached >1 nM levels in brain parenchyma.CONCLUSIONS:
These data indicate that pioglitazone crosses the blood-brain barrier and has antineoplastic effects in this glioma xenograft model and may be of potential use in treatment of malignant gliomas.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Barreira Hematoencefálica
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Tiazolidinedionas
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PPAR gama
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Glioma
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos