Peroxisome proliferator-activated receptor γ agonist pioglitazone inhibits β-catenin-mediated glioma cell growth and invasion

Gliomas are the most common primary tumors of the central nervous system. Rapid proliferation and diffuse brain invasion of these tumors are likely to determine the unfavorable prognosis. Recent studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) can induce differentiation and inhibit proliferation of several cancer cells. In this study, we identified pioglitazone, one PPAR gamma ligand in particular, suppressed human glioma cells proliferation, migration, and induced glioma cells apoptosis. Concomitantly, expression level of beta-catenin protein, a key molecule in carcinogenesis, was decreased in glioma cells treated with pioglitazone. Noteworthy, knockdown of beta-catenin expression using siRNA technology mimicked the anti-neoplastic potency of pioglitazone. These results indicate that beta-cateninz is one of the mediators for pioglitazone to suppress glioma cells growth and invasion. Due to its capacity to counteract beta-catenin and glioma cell proliferation and migration, pioglitazone represents a promising drug for adjuvant therapy of glioma and other highly migratory tumor entities.