Fujihara, Toshitaka Tokushima University Tokushima University Educator and Researcher Directory
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Matsuzaki, Kazuhito Tokushima University
Kitazato, Keiko T. Tokushima University
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Takagi, Yasushi Tokushima University Tokushima University Educator and Researcher Directory
Thesis or Dissertation
Background: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1.
Methods: GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination.
Results: Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway.
Conclusions: Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.
Journal of Neuro-Oncology
Springer Science+Business Media, LLC
This is a post-peer-review, pre-copyedit version of an article published in Journal of Neuro-Oncology. The final authenticated version is available online at: https://doi.org/10.1007/s11060-018-2894-5
© Springer Science+Business Media, LLC, part of Springer Nature 2018
|DOI (Published Version)|
|URL ( Publisher's Version )|
k3239_abstract_review.pdf 253 KB
k3239_fulltext.pdf 421 KB
|MEXT report number||
Doctor of Medical Science