1. 4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/ Akt/ mTOR-independent pathway.
- Author
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Zhu, Hui‐Li, Xie, Si‐Ming, Fang, Mao, Zhang, Ji‐Jun, Weng, Ze‐Ping, and Zhong, Xue‐Yun
- Subjects
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DRUG therapy , *GLIOMA treatment , *DRUG resistance , *MULTIPLE tumors , *CARMUSTINE - Abstract
Drug resistance is one of the most formidable obstacles for treatment of glioma. Eukaryotic initiation factor 4E-binding protein ( 4E-BP1), a key component in the rate-limiting step of protein translation initiation, is closely associated with poor prognosis in multiple tumor types. However, it is unclear whether 4E-BP1 is involved in the drug resistance of human glioma. Herein we show that the expression of 4E-BP1 in human SWOZ2- BCNU drug-resistant glioma cells is significantly lower than that of the parent SWOZ2 cell line. Moreover, down-regulation of 4E-BP1 by short interfering RNA significantly impaired the sensitivity of SWOZ2 and U251 cells to carmustine ( BCNU). Furthermore, overexpression of 4E-BP1 with plasmid transfection regained this sensitivity. Clinical studies showed that the expression levels of 4E-BP1 in primary glioma tissues were markedly higher than those of recrudescent glioma tissues. Taken together, our results suggest that 4E-BP1 is a novel protein that contributes to acquired drug resistance and it may be a potential target for reversing drug resistance in human glioma. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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