Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-кB/MDR1 pathway

• Material Type: 博士論文
• Title: Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-кB/MDR1 pathway
• Author/Editor: Shono, Kenji; Mizobuchi, Yoshifumi; Yamaguchi, Izumi; Nakajima, Kohei; Fujiwara, Yuri; Fujihara, Toshitaka; Kitazato, Keiko; Matsuzaki, Kazuhito; Uto, Yoshihiro; Sampetrean, Oltea; Saya, Hideyuki; Takagi, Yasushi
• Author Heading: Shono, Kenji; Mizobuchi, Yoshifumi; Yamaguchi, Izumi; Nakajima, Kohei; Fujiwara, Yuri; Fujihara, Toshitaka; Kitazato, Keiko; Matsuzaki, Kazuhito; Uto, Yoshihiro; Sampetrean, Oltea; Saya, Hideyuki; Takagi, Yasushi
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2021-07-23
• Publication Date (W3CDTF): 2021-07-23
• Alternative Title: 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
• Periodical title: Scientific Reports
• No. or year of volume/issue: 11
• Volume: 11
• Pages: 15105-
• ISSN (Periodical Title): ISSN : 2045-2322
• Degree grantor/type: 徳島大学
• Date Granted: 2021-10-28
• Dissertation Number: 甲第3560号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Sonodynamic therapy; PpIX; stem cell; stem cell-bearing glioma model
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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/
• Related Material (DOI): 10.1038/s41598-021-93896-0
• 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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