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Combination gene therapy with PTEN and EGFR siRNA suppresses U251 malignant glioma cell growth in vitro and in vivo

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Abstract

The over-expression/amplification of the epidermal growth factor receptor (EGFR) gene and mutation/deletion of tumor suppressor PTEN gene are main genetic changes identified in glioblastomas. These two genetic changes play a critical role in the formation of many malignant tumors and have been shown to be the important therapeutic targets. In this study, we used an expression plasmid that expresses small hairpin RNA-targeting sequences of human EGFR and wild-type PTEN cDNA to examine the growth inhibitive effects in U251 glioma cells. It was found that down-regulation of EGFR expression and up-regulation of PTEN expression resulted in the suppression of cell proliferation, arrest of cell cycle, reduction in cell invasion and promotion of cell apoptosis in vitro. In addition, the growth of the subcutaneous U251 glioma in the nude mice treated with expression plasmid was significantly inhibited. Our results demonstrated that the expression plasmid could exert proliferation and invasion inhibition effects on U251 cells in vitro and in vivo. It suggested that combinatory gene therapy targeting EGFR and PTEN would be a new strategy in gene therapy of glioblastoma.

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Acknowledgments

This work was supported by Program for New Century Excellent Talents in University (NCET-07-0615) and Key Project Foundation from Tianjin Science and Technology Committee (No. 09JCZDJC17600) to which the authors wish to express their thanks.

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Authors and Affiliations

  1. Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital and Lab of Neuro-oncology, 154 An-Shan Road, Heping District, 300052, Tianjin, People’s Republic of China

    Lei Han, An-ling Zhang, Peng Xu, Xiao Yue, Yang Yang, Guang-xiu Wang, Zhi-fan Jia, Pei-yu Pu & Chun-sheng Kang

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  1. Lei Han
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  2. An-ling Zhang
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  3. Peng Xu
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  4. Xiao Yue
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  7. Zhi-fan Jia
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  9. Chun-sheng Kang
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Correspondence to Chun-sheng Kang.

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Han, L., Zhang, Al., Xu, P. et al. Combination gene therapy with PTEN and EGFR siRNA suppresses U251 malignant glioma cell growth in vitro and in vivo. Med Oncol 27, 843–852 (2010). https://doi.org/10.1007/s12032-009-9295-8

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  • DOI: https://doi.org/10.1007/s12032-009-9295-8

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