神戸大学附属図書館デジタルアーカイブ
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https://hdl.handle.net/20.500.14094/90009162
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2024-03-29
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90009162 (fulltext)
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メタデータID
90009162
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open access
出版タイプ
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タイトル
Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells
著者
Salah, Mohammed ; Akasaka, Hiroaki ; Shimizu, Yasuyuki ; Morita, Kenta ; Nishimura, Yuya ; Kubota, Hikaru ; Kawaguchi, Hiroki ; Sogawa, Tomomi ; Mukumoto, Naritoshi ; Ogino, Chiaki ; Sasaki, Ryohei
著者名
Salah, Mohammed
著者ID
A1164
研究者ID
1000020707161
著者名
Akasaka, Hiroaki
赤坂, 浩亮
アカサカ, ヒロアキ
所属機関名
医学部附属病院
著者ID
A2789
研究者ID
1000080824234
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/profile/ja.12d8cf6fe4614de5520e17560c007669.html
著者名
Shimizu, Yasuyuki
清水, 康之
シミズ, ヤスユキ
所属機関名
医学部附属病院
著者ID
A2788
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/profile/ja.4c6fa0d9aef47a7b520e17560c007669.html
著者名
Morita, Kenta
森田, 健太
モリタ, ケンタ
所属機関名
工学研究科
著者ID
A1345
研究者ID
1000040728218
著者名
Nishimura, Yuya
西村, 勇哉
ニシムラ, ユウヤ
所属機関名
科学技術イノベーション研究科
著者名
Kubota, Hikaru
著者名
Kawaguchi, Hiroki
著者名
Sogawa, Tomomi
著者ID
A2247
研究者ID
1000070634278
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/profile/ja.79fcee28d118d94d520e17560c007669.html
著者名
Mukumoto, Naritoshi
椋本, 成俊
ムクモト, ナリトシ
所属機関名
医学部附属病院
著者ID
A0339
研究者ID
1000000313693
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/profile/ja.cb7c84b4e252c367520e17560c007669.html
著者名
Ogino, Chiaki
荻野, 千秋
オギノ, チアキ
所属機関名
工学研究科
著者ID
A1363
研究者ID
1000030346267
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/profile/ja.f5e9afd9968a7ac8520e17560c007669.html
著者名
Sasaki, Ryohei
佐々木, 良平
ササキ, リョウヘイ
所属機関名
医学部附属病院
収録物名
Journal of Experimental & Clinical Cancer Research
巻(号)
41(1)
ページ
146
出版者
BMC
刊行日
2022-04-15
公開日
2022-04-26
抄録
Background Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs. Methods CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO2NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo. Results It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway. Conclusions Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.
キーワード
Radioresistance
Pancreatic cancer stem cells
Titanium peroxide nanoparticles
Radiosensitizers
Reactive oxygen species
AKT
カテゴリ
医学部附属病院
科学技術イノベーション研究科
工学研究科
学術雑誌論文
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© The Author(s) 2022.
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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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資源タイプ
journal article
言語
English (英語)
eISSN
1756-9966
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関連情報
DOI
https://doi.org/10.1186/s13046-022-02358-6
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