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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 8/2020

01-08-2020 | Glioblastoma | Research Article

IKBKE enhances TMZ-chemoresistance through upregulation of MGMT expression in glioblastoma

Authors: G. Guo, Y. Sun, R. Hong, J. Xiong, Y. Lu, Y. Liu, J. Lu, Z. Zhang, C. Guo, Y. Nan, Q. Huang

Published in: Clinical and Translational Oncology | Issue 8/2020

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Abstract

Purpose

Glioblastoma multiforme (GBM) is the most common and aggressive malignant type of brain tumor. Despite advances in diagnosis and therapy, the prognosis of patients with GBM has remained dismal. Multidrug resistance and high recurrence are two of the major challenges in successfully treating brain tumors. IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is a major oncogenic protein in tumors and can inhibit glioblastoma cell proliferation, migration, and tumorigenesis. Our study aimed to investigate the mechanism of IKBKE enhancing the resistance of glioma cells to temozolomide.

Methods

For the in vitro experiments, LN18 and U118 glioblastoma cells were treated with a combination of sh/oe-IKBKE lentivirus and TMZ. Cell proliferation was determined by the EdU assay and colony formation assays. Apoptosis was analyzed by the TUNEL assay. In vivo, LN18 NC and LN18 sh-IKBKE cells were implanted into the cerebrums of nude mice to detect the effect of combination therapy. The protein and mRNA levels were assayed by western blot, immunohistochemistry, and qRT-PCR.

Results

In this study, we demonstrated that IKBKE enhances the resistance of glioblastoma cells to temozolomide (TMZ) by activating the AKT/NF-κB signaling pathway to upregulate the expression of the DNA repair enzyme o6-methylguanine-dna methyltransferase (MGMT). In glioblastoma cells, IKBKE knockdown enhances apoptosis and suppresses cell proliferation, clone formation, and tumor development in vivo induced by TMZ. However, overexpression of IKBKE reduces the effects of TMZ.

Conclusion

Our studies suggest that inhibition of IKBKE can enhance the therapeutic effect of TMZ on GBM in vitro and in vivo, providing new research directions and therapeutic targets for the treatment of GBM.
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Metadata
Title
IKBKE enhances TMZ-chemoresistance through upregulation of MGMT expression in glioblastoma
Authors
G. Guo
Y. Sun
R. Hong
J. Xiong
Y. Lu
Y. Liu
J. Lu
Z. Zhang
C. Guo
Y. Nan
Q. Huang
Publication date
01-08-2020
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 8/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02251-3

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