Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model

• Material Type: 博士論文
• Title: Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model
• Author/Editor: Fujihara, Toshitaka; Mizobuchi, Yoshifumi; Nakajima, Kohei; Kageji, Teruyoshi; Matsuzaki, Kazuhito; Kitazato, Keiko T.; Otsuka, Ryotaro; Hara, Keijiro; Mure, Hideo; Okazaki, Toshiyuki; Kuwayama, Kazuyuki; Nagahiro, Shinji; Takagi, Yasushi
• Author Heading: Fujihara, Toshitaka; Mizobuchi, Yoshifumi; Nakajima, Kohei; Kageji, Teruyoshi; Matsuzaki, Kazuhito; Kitazato, Keiko T.; Otsuka, Ryotaro; Hara, Keijiro; Mure, Hideo; Okazaki, Toshiyuki; Kuwayama, Kazuyuki; Nagahiro, Shinji; Takagi, Yasushi
• Publication, Distribution, etc.: Springer Science+Business Media, LLC
• Publication Date: 2018-05-19
• Publication Date (W3CDTF): 2018-05-19
• Alternative Title: 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
• Periodical title: Journal of Neuro-Oncology
• No. or year of volume/issue: 139 2
• Volume: 139
• Issue: 2
• Pages: 323-332
• ISSN (Periodical Title): ISSN : 0167-594X; ISSN : 1573-7373
• Degree grantor/type: 徳島大学
• Date Granted: 2018-10-25
• Dissertation Number: 甲第3239号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: DKK3; MDR1; Akt; glioblastoma; temozolomide
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © Springer Science+Business Media, LLC, part of Springer Nature 2018
• Related Material (DOI): 10.1007/s11060-018-2894-5
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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