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4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/ Akt/ mTOR-independent pathway.
- Source :
-
Neuropathology . Jun2014, Vol. 34 Issue 3, p227-235. 9p. - Publication Year :
- 2014
-
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]
- Subjects :
- *DRUG therapy
*GLIOMA treatment
*DRUG resistance
*MULTIPLE tumors
*CARMUSTINE
Subjects
Details
- Language :
- English
- ISSN :
- 09196544
- Volume :
- 34
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Neuropathology
- Publication Type :
- Academic Journal
- Accession number :
- 96287902
- Full Text :
- https://doi.org/10.1111/neup.12085