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Rosiglitazone Suppresses Glioma Cell Growth and Cell Cycle by Blocking the Transforming Growth Factor-Beta Mediated Pathway

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Abstract

Glioma is one of the most malignant tumors in the central nervous system. As a peroxisome proliferator-activated receptor γ (PPAR-γ) activator, the thiazolidinediones (TZDs) induce growth arrest and cell death in a broad spectrum of tumor cells. In this study, we investigated the role of rosiglitazone in glioma cells. We found that rosiglitazone, a member of TZDs, suppresses growth of human glioma cell lines U87 and U251. Rosiglitazone also induces cell cycle arrest and apoptosis, which may be the mechanism of its anti-proliferation effect. Next, we found that rosiglitazone suppresses the expression of TGF-beta and its receptor TGF-betaR2, and suppresses phosphorylation of Smad3. Rosiglitazone also inhibits formation of the Smad3/Smad4 complex. Furthermore, Rosiglitazone affects the expression of Smad3/Smad4 associated regulators of gene expression, including p21 and c-Myc. These results suggest that rosiglitazone suppresses growth and cell cycle of human glioma cells by blocking the TGF-beta mediated pathway.

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Acknowledgments

This work was supported by the grant from Tianjin Municipal Health Bureau (07KC79), Tianjin, China.

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Authors and Affiliations

  1. Department of Neuro-oncology & Neurosurgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Peng Wang, Qiang Yin & Wenliang Li

  2. Department of Immunology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tiyuanbei, Huanhuxi Road, Tianjin, 300060, Hexi District, China

    Jinpu Yu, Xiubao Ren & Xishan Hao

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  1. Peng Wang
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  2. Jinpu Yu
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  3. Qiang Yin
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  4. Wenliang Li
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Correspondence to Xishan Hao.

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Wang, P., Yu, J., Yin, Q. et al. Rosiglitazone Suppresses Glioma Cell Growth and Cell Cycle by Blocking the Transforming Growth Factor-Beta Mediated Pathway. Neurochem Res 37, 2076–2084 (2012). https://doi.org/10.1007/s11064-012-0828-8

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