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

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Abstract

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 γ (PPARγ) can induce differentiation and inhibit proliferation of several cancer cells. In this study, we identified pioglitazone, one PPARγ ligand in particular, suppressed human glioma cells proliferation, migration, and induced glioma cells apoptosis. Concomitantly, expression level of β-catenin protein, a key molecule in carcinogenesis, was decreased in glioma cells treated with pioglitazone. Noteworthy, knockdown of β-catenin expression using siRNA technology mimicked the anti-neoplastic potency of pioglitazone. These results indicate that β-catenin is one of the mediators for pioglitazone to suppress glioma cells growth and invasion. Due to its capacity to counteract β-catenin and glioma cell proliferation and migration, pioglitazone represents a promising drug for adjuvant therapy of glioma and other highly migratory tumor entities.

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Abbreviations

PPARγ:

Peroxisome proliferator-activated receptor

GW9662:

2-Chloro-5-nitrobenzanilide

MMP-2:

Matrix metalloproteinase 2

DMSO:

Dimethyl sulfoxide

DMEM:

Dulbecco’s modified Eagle’s medium

PBS:

Phosphate-buffered saline

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 30770488, 30870320, 31070723 and 81070275); Natural Science Foundation of Jiangsu province (BK2009156, BK2009157, and BK2009161).

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Authors and Affiliations

  1. Department of Neurosurgery, Affiliated Second Hospital of Suzhou University, Suzhou, 215004, People’s Republic of China

    Zhengqiang Wan, Yuyuan Ma & Qing Lan

  2. Department of Neurosurgery, Fourth Affiliated Yancheng Hospital of Nantong University, Yancheng, People’s Republic of China

    Zhengqiang Wan

  3. Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, 226001, People’s Republic of China

    Wei Shi, Bai Shao, Jinlong Shi, Aiguo Shen & Jian Chen

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  1. Zhengqiang Wan
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Correspondence to Jian Chen or Qing Lan.

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Wan, Z., Shi, W., Shao, B. et al. Peroxisome proliferator-activated receptor γ agonist pioglitazone inhibits β-catenin-mediated glioma cell growth and invasion. Mol Cell Biochem 349, 1–10 (2011). https://doi.org/10.1007/s11010-010-0637-9

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  • DOI: https://doi.org/10.1007/s11010-010-0637-9

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