Combination gene therapy with PTEN and EGFR siRNA suppresses U251 malignant glioma cell growth in vitro and in vivo |
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Authors: | 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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Institution: | (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; |
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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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