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Article

Inhibition of eIF4F complex loading inhibits the survival of malignant glioma

  • Authors:
    • Qiu‑Feng Dong
    • Zhi‑Feng Yan
    • Peng‑Qi Li
    • Xin Yang
    • Jun‑Li Huo
    • Hai‑Ning Zhen
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
  • Pages: 2399-2407
    |
    Published online on: July 20, 2018
       https://doi.org/10.3892/or.2018.6587
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Abstract

The eukaryotic initiation factor (eIF)4E‑binding proteins (4E‑BPs) regulate cap‑dependent protein translation and control the assembly of the eIF4F complex. In the present study, a phosphorylation‑deficient truncated 4E‑BP2 (eIF4FD) was constructed into the eukaryotic expression vector pSecTag2, and the in vitro and in vivo effects on malignant glioma survival were determined through inhibiting eIF4F complex assembly. Cell cycle distribution analysis and TUNEL staining show that overexpression of eIF4FD suppressed cell proliferation and induced apoptosis in U251 cells. Western blotting showed that the cell cycle‑related genes cyclin D1 and C‑myc, and anti‑apoptotic genes B‑cell lymphoma 2 (Bcl‑2), Bcl‑extra large and survivin were reduced following the overexpression of eIF4FD. Furthermore, eIF4FD suppressed glioma vascularization via reductions in the expression of β‑catenin and vascular endothelial growth factor. In the orthotopic xenograft model, the stable expression of eIF4FD in U251 cells attenuated cell growth and increased the rate of apoptosis. Accordingly, pSecTag2‑PTD‑eIF4FD injection via the tail vein of mice also lead to cell growth inhibition and the induction of apoptosis. Therefore, the study showed that phosphorylation‑deficient truncated 4E‑BP2 efficiently inhibited eIF4E and prevented the formation of the eIF4F complex, which further contributed to the inhibition of cell proliferation and vascularization, and the induction of apoptosis. Therefore, the 4E‑BP2‑based phosphorylation‑deficient truncation designed in the present study may represent a novel approach for the targeted therapy of human malignant glioma though inhibition of the translation initiation complex.
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Copy and paste a formatted citation
Spandidos Publications style
Dong QF, Yan ZF, Li PQ, Yang X, Huo JL and Zhen HN: Inhibition of eIF4F complex loading inhibits the survival of malignant glioma. Oncol Rep 40: 2399-2407, 2018.
APA
Dong, Q., Yan, Z., Li, P., Yang, X., Huo, J., & Zhen, H. (2018). Inhibition of eIF4F complex loading inhibits the survival of malignant glioma. Oncology Reports, 40, 2399-2407. https://doi.org/10.3892/or.2018.6587
MLA
Dong, Q., Yan, Z., Li, P., Yang, X., Huo, J., Zhen, H."Inhibition of eIF4F complex loading inhibits the survival of malignant glioma". Oncology Reports 40.4 (2018): 2399-2407.
Chicago
Dong, Q., Yan, Z., Li, P., Yang, X., Huo, J., Zhen, H."Inhibition of eIF4F complex loading inhibits the survival of malignant glioma". Oncology Reports 40, no. 4 (2018): 2399-2407. https://doi.org/10.3892/or.2018.6587
Copy and paste a formatted citation
x
Spandidos Publications style
Dong QF, Yan ZF, Li PQ, Yang X, Huo JL and Zhen HN: Inhibition of eIF4F complex loading inhibits the survival of malignant glioma. Oncol Rep 40: 2399-2407, 2018.
APA
Dong, Q., Yan, Z., Li, P., Yang, X., Huo, J., & Zhen, H. (2018). Inhibition of eIF4F complex loading inhibits the survival of malignant glioma. Oncology Reports, 40, 2399-2407. https://doi.org/10.3892/or.2018.6587
MLA
Dong, Q., Yan, Z., Li, P., Yang, X., Huo, J., Zhen, H."Inhibition of eIF4F complex loading inhibits the survival of malignant glioma". Oncology Reports 40.4 (2018): 2399-2407.
Chicago
Dong, Q., Yan, Z., Li, P., Yang, X., Huo, J., Zhen, H."Inhibition of eIF4F complex loading inhibits the survival of malignant glioma". Oncology Reports 40, no. 4 (2018): 2399-2407. https://doi.org/10.3892/or.2018.6587
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