BI-01 * 4EBP1 PARTICIPATES IN CISPLATIN RESISTANCE OF HUMAN GLIOMA CELLS THROUGH PI3K/AKT/mTOR PATHWAY

Abstract

BACKGROUND: The oncogenic activation of mTOR pathway is considered to be crucial for tumorigenesis and tumor progression in glioblastoma (GBM). But GBMs are strikingly resistant to mTOR-targeted therapy. We observed the change of 4EBP1 gene expression is significantly higher in primary GBMs than recurrent GBMs. In this study, we focused on 4EBP1 potential mechanisms of action in PI3K/AKT/mTOR pathway. METHODS: U251 cell lines and U251/BCNU cell lines were treated with rapamycin and LY294002, and the cell growth changes in response to subsequent cisplatin treatment was observed. QPCR was performed to detect 4EBP1 mRNA expression in the cells. RESULTS: Blocking PI3K/AKT/mTOR pathway by rapamycin and LY294002 significantly reduced drug resistance of both U251 and U251/BCNU cells to cisplatin and obviously decreased the expression of 4EBP1 gene mRNA (p <0.05). CONCLUSIONS: 4EBP1 gene is located downstream of the PI3K/AKT/mTOR pathway, which might be one of the mechanisms of 4EBP1 to cause cisplatin resistance in the glioma cells.