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ID 112895
Title Alternative
膠芽腫細胞およびマウス背部皮下モデルにおいて,アデノウイルスベクターを用いたDKK3の導入はAkt/NFκB経路を介してMDR1の発現を抑制し,テモゾロミドによる抗腫瘍効果を増強する
Author
Matsuzaki, Kazuhito Tokushima University
Kitazato, Keiko T. Tokushima University
Otsuka, Ryotaro Tokushima University
Keywords
DKK3
MDR1
Akt
glioblastoma
temozolomide
Content Type
Thesis or Dissertation
Description
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 Title
Journal of Neuro-Oncology
ISSN
0167594X
15737373
NCID
AA10633712
Publisher
Springer Science+Business Media, LLC
Volume
139
Issue
2
Start Page
323
End Page
332
Published Date
2018-05-19
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Toshitaka Fujiharaの学位論文として提出され,学位審査・授与の対象となっている。
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
Rights
© Springer Science+Business Media, LLC, part of Springer Nature 2018
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3239号
Diploma Number
甲医第1388号
Granted Date
2018-10-25
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences