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Anti-inflammatory Effects of Atorvastatin by Suppressing TRAF3IP2 and IL-17RA in Human Glioblastoma Spheroids Cultured in a Three-dimensional Model: Possible Relevance to Glioblastoma Treatment

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An Erratum to this article was published on 06 May 2017

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Abstract

Glioblastoma multiform (GBM) is a primary malignant brain tumor with a few therapeutic targets available for it. The interaction between the immune system and glioma is an important factor that could lead to novel therapeutic approaches to fight glioma. In this study, we investigated in vitro anti-inflammatory and apoptotic activity of atorvastatin in different concentrations 1, 5, and 10 μM on glioma spheroid cells cultured in a three-dimensional model in fibrin gel that indicate the complex in vivo microenvironment better than a simple two-dimensional cell culture. A mechanistic insight into the role of IL-17RA, TRAF3IP2, and apoptotic genes in progression of glioma could provide an important way for therapy of malignant tumors with manipulation of this inflammatory axis. To reach for these aims, after 24 and 48 h exposure with different concentrations of atorvastatin, caspase-8, caspase-3, Bcl-2, TRAF3IP2, and IL-17RA gene expression were assayed. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and cell cycle assay were used for evaluating the cell apoptosis and proliferation. The results showed that atorvastatin has anti-inflammatory and apoptotic effects against glioma spheroids. Atorvastatin induced the expression of caspase-3 and caspase-8 and downregulated the expression of Bcl-2, TRAF3IP2, and IL-17RA especially at 10 μM concentration. These effects are dose dependent. The most likely mechanisms are the inhibition of inflammation by IL-17RA interaction with TRAF3IP2 and NF-κB signaling pathway. Finally, these results suggest that atorvastatin could be used as an anti-cancer agent for glioblastoma treatment.

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  • 06 May 2017

    An erratum to this article has been published.

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Acknowledgments

We thank the Iran National Science Foundation (INSF) for the financial support (grant number 93051217) and Tehran University of Medical Sciences for this research.

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Authors and Affiliations

  1. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Neda Bayat, Abbas Norouzi-Javidan, Hooshang Saberi & Jafar Ai

  2. Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Somayeh Ebrahimi-Barough, Mohammad Mehdi Mokhtari Ardakan, Mostafa Soleimannejad & Jafar Ai

  3. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Arman Ai

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  1. Neda Bayat
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  2. Somayeh Ebrahimi-Barough
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Correspondence to Somayeh Ebrahimi-Barough or Jafar Ai.

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Dr. Jafar Ai is the first corresponding author.

An erratum to this article is available at https://doi.org/10.1007/s12035-017-0577-4.

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Bayat, N., Ebrahimi-Barough, S., Norouzi-Javidan, A. et al. Anti-inflammatory Effects of Atorvastatin by Suppressing TRAF3IP2 and IL-17RA in Human Glioblastoma Spheroids Cultured in a Three-dimensional Model: Possible Relevance to Glioblastoma Treatment. Mol Neurobiol 55, 2102–2110 (2018). https://doi.org/10.1007/s12035-017-0445-2

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