Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro

  • Authors:
    • Katja Storch
    • Andre Sagerer
    • Nils Cordes
  • View Affiliations

  • Published online on: January 27, 2015     https://doi.org/10.3892/or.2015.3753
  • Pages: 2009-2016
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Abstract

Glioblastoma multiforme (GBM) is a highly aggressive and extremely lethal cancer and novel molecular therapies are required for optimized multimodal therapy regimes. While focal adhesion kinase (FAK) is regarded as a therapeutic target, its radiosensitizing potential remains to be elucidated in glioblastoma. Thus, FAK was inhibited using the pharmaco­logical inhibitor TAE226 and cytotoxicity and radiosensitization of glioblastoma cells were investigated in vitro. Monolayer and suspension cell cultures of a panel of glioblastoma cell lines (A172, LN229, U87MG, U138MG, U343MG, DD-HT7607, and DD-T4) were treated with increasing TAE226 concentrations (0-10 µM) alone or in combination with X-rays (0-6 Gy). Subsequently, clonogenic cell survival, expression and the phosphorylation of FAK downstream signaling, apoptosis and autophagy were analyzed. Efficient FAK inhibition by TAE226 mediated significant cytotoxicity and reduced sphere formation in a dose- and time-dependent manner. Two out of seven glioblastoma cell lines showed radiosensitization. Apoptotic induction by TAE226 was cell line-dependent. The results demonstrated that pharmacological FAK inhibitor TAE226 efficiently reduced clonogenicity and sphere formation in glioblastoma cells without generally modifying their radiosensitivity. However, future studies are necessary to define the potential of FAK inhibition by TAE226 or other pharmacological inhibitors in combination with radiochemotherapy.
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April-2015
Volume 33 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Storch K, Sagerer A and Cordes N: Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro. Oncol Rep 33: 2009-2016, 2015
APA
Storch, K., Sagerer, A., & Cordes, N. (2015). Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro. Oncology Reports, 33, 2009-2016. https://doi.org/10.3892/or.2015.3753
MLA
Storch, K., Sagerer, A., Cordes, N."Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro". Oncology Reports 33.4 (2015): 2009-2016.
Chicago
Storch, K., Sagerer, A., Cordes, N."Cytotoxic and radiosensitizing effects of FAK targeting in human glioblastoma cells in vitro". Oncology Reports 33, no. 4 (2015): 2009-2016. https://doi.org/10.3892/or.2015.3753