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.
Med Oncol. 2010 Sep;27(3):843-52. doi: 10.1007/s12032-009-9295-8. Epub 2009 Aug 29.
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.
表皮生长因子受体（EGFR）基因的过度表达/扩增和肿瘤抑制基因 PTEN 的突变/缺失是胶质母细胞瘤中鉴定的主要遗传改变。这两种遗传改变在许多恶性肿瘤的形成中起着关键作用，并且已被证明是重要的治疗靶点。在这项研究中，我们使用表达质粒表达针对人 EGFR 和野生型 PTEN cDNA 的小发夹 RNA 靶向序列，以研究其对 U251 神经胶质瘤细胞的生长抑制作用。结果发现，下调 EGFR 表达和上调 PTEN 表达导致细胞增殖受到抑制，细胞周期停滞，细胞侵袭减少，并促进细胞凋亡。此外，用表达质粒处理的裸鼠皮下 U251 神经胶质瘤的生长明显受到抑制。我们的结果表明，表达质粒可在体外和体内对 U251 细胞发挥增殖和侵袭抑制作用。这表明针对 EGFR 和 PTEN 的联合基因治疗可能成为胶质母细胞瘤基因治疗的一种新策略。
