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
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Author |
Nakajima, Kohei
Tokushima University
Tokushima University Educator and Researcher Directory
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Matsuzaki, Kazuhito
Tokushima University
Kitazato, Keiko T.
Tokushima University
Otsuka, Ryotaro
Tokushima University
Mure, Hideo
Tokushima University
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Keywords | DKK3
MDR1
Akt
glioblastoma
temozolomide
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Content Type |
Thesis or Dissertation
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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
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ISSN | 0167594X
15737373
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NCID | AA10633712
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Publisher | Springer Science+Business Media, LLC
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Volume | 139
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Issue | 2
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Start Page | 323
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End Page | 332
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Published Date | 2018-05-19
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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
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3239号
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Diploma Number | 甲医第1388号
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Granted Date | 2018-10-25
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
University Hospital
Medical Sciences
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