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Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

Cancer Gene Therapy volume 13, pages 530–538 (2006)Cite this article

Abstract

Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400–2420) and the 3′-coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense- and siRNA-treated groups than the control groups. Our results demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.

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Acknowledgements

This work is supported by National Natural Science Foundation of China, Grant Number 30400461; Committee of Tianjin Science and Technology, Grant Number 023111511-2 and 05YFJZJC1002.

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Authors and Affiliations

  1. Department of Neurosurgery, Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, People's Republic of China

    C-S Kang, Z-Y Zhang, Z-F Jia, G-X Wang, M-Z Qiu & P-Y Pu

  2. Institute of Nanobiotechnology, College of Material and Engineering, Tianjin University, Tianjin, People's Republic of China

    C-S Kang & J Chang

  3. Department of Neurology, Tianjin Medical University General Hospital and Laboratory of Neuro-Pathology, Tianjin Neurological Institute, Tianjin, People's Republic of China

    H-X Zhou & S-Z Yu

  4. Department of Neurology, William T. Gossett Neurology Laboratories, Henry Ford Health System, Detroit, MI, USA

    H Jiang

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  1. C-S Kang
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Correspondence to P-Y Pu.

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Kang, CS., Zhang, ZY., Jia, ZF. et al. Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo. Cancer Gene Ther 13, 530–538 (2006). https://doi.org/10.1038/sj.cgt.7700932

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  • DOI: https://doi.org/10.1038/sj.cgt.7700932

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