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ID 116448
Title Alternative
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
Author
Shono, Kenji Tokushima University
Fujiwara, Yuri Tokushima University
Kitazato, Keiko Tokushima University
Matsuzaki, Kazuhito Tokushima University
Sampetrean, Oltea Keio University
Saya, Hideyuki Keio University
Keywords
Sonodynamic therapy
PpIX
stem cell
stem cell-bearing glioma model
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
11
Start Page
15105
Published Date
2021-07-23
Remark
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。
Rights
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/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3560号
Diploma Number
甲医第1512号
Granted Date
2021-10-28
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Bioscience and Bioindustry
Medical Sciences