アクセス数 : ?
ダウンロード数 : ?
ID 116448
タイトル別表記
Akt/NF-кB/MDR1経路の抑制による脳腫瘍細胞内のPpIXの上昇はグリオーマ幹細胞移植脳腫瘍モデルマウスの超音波力学療法の効果を増強する
著者
庄野, 健児 徳島大学大学院医科学教育部(医学専攻)
Fujiwara, Yuri Tokushima University
Kitazato, Keiko Tokushima University
Matsuzaki, Kazuhito Tokushima University
Sampetrean, Oltea Keio University
Saya, Hideyuki Keio University
キーワード
Sonodynamic therapy
PpIX
stem cell
stem cell-bearing glioma model
資料タイプ
学位論文
抄録
Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
11
開始ページ
15105
発行日
2021-07-23
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Kenji Shono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。
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3560号
学位記番号
甲医第1512号
学位授与年月日
2021-10-28
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
生物資源系
医学系