The PPARγ agonist pioglitazone crosses the blood-brain barrier and reduces tumor growth in a human xenograft model. Academic Article uri icon

Overview

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.

publication date

  • January 29, 2013

Research

keywords

  • Blood-Brain Barrier
  • Brain Neoplasms
  • Glioma
  • PPAR gamma
  • Thiazolidinediones

Identity

Scopus Document Identifier

  • 84878865441

Digital Object Identifier (DOI)

  • 10.1007/s00280-013-2084-2

PubMed ID

  • 23358645

Additional Document Info

volume

  • 71

issue

  • 4