title: 4E-BP1 regulates the sensitivity of human glioma cells to chemotherapy through PI3K/Akt/mTOR-independent pathway.
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.
authors.affiliation: The First Affiliated Hospital of Jinan University, Guangzhou, China; Department of Pathology, Medical College of Jinan University, Guangzhou, China.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Zhu
authors.forename: Si-Ming
authors.initials: SM
authors.lastname: Xie
authors.forename: Mao
authors.initials: M
authors.lastname: Fang
authors.forename: Ji-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Ze-Ping
authors.initials: ZP
authors.lastname: Weng
authors.forename: Xue-Yun
authors.initials: XY
authors.lastname: Zhong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000502:physiology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use*; D002330:Carmustine / Q000494:pharmacology / Q000627:therapeutic use; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018906:Antineoplastic Agents, Alkylating; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D002330:Carmustine
keywords: 4E-BP1; BCNU; chemotherapy; drug resistance; glioma