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ID 118302
タイトル別表記
青色光は滑膜肉腫に対して活性酸素種によるミトコンドリア機能障害を起こし、アポトーシスとオートファジーを誘導する
著者
竹内, 誠 徳島大学大学院医学研究科(医学専攻) 徳島大学 教育研究者総覧
川口, 真司 Tokushima University
キーワード
synovial sarcoma
blue light
reactive oxygen species
apoptosis
autophagy
mitochondria
資料タイプ
学位論文
抄録
Background: Synovial sarcoma (SS) has limited treatment options and there is an urgent need to develop a novel therapeutic strategy to treat SS. Blue light (BL) has been shown to inhibit the growth of several cancer cells. However, the efficacy of BL in soft tissue sarcomas such as SS has not been demonstrated, and the detailed mechanism underlying the antitumor activity of BL is not fully understood. In this study, we investigated the antitumor effect of BL on SS.
Methods: Human SS cell lines were continuously irradiated with BL using light-emitting diodes (LEDs) in an incubator for in vitro analysis. The chicken chorioallantoic membrane (CAM) tumors and xenograft tumors in mice were subjected to daily BL irradiation with LEDs.
Results: BL caused growth inhibition of SS cells and histological changes in CAM tumors. BL also suppressed the migration and invasion abilities of SS cells. The type of cell death in SS cells was revealed to be apoptosis. Furthermore, BL induced excessive production of reactive oxygen species (ROS) in mitochondria, resulting in oxidative stress and malfunctioned mitochondria. Reducing the production of ROS using N-acetylcysteine (NAC), a ROS scavenger, attenuated the inhibitory effect of BL on SS cells and mitochondrial dysfunction. In addition, BL induced autophagy, which was suppressed by the administration of NAC. The autophagy inhibitor of 3-methyladenine and small interfering RNA against the autophagy marker light chain 3B facilitated apoptotic cell death. Moreover, BL suppressed tumor growth in a mouse xenograft model.
Conclusion: Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.
掲載誌名
Cancer Medicine
ISSN
20457634
出版者
John Wiley & Sons
12
8
開始ページ
9668
終了ページ
9683
発行日
2023-02-01
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Makoto Takeuchi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 is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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3704号
学位記番号
甲医第1574号
学位授与年月日
2023-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院
生物資源系
先端酵素学研究所