Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells

Horie Ryosuke; 堀江 亮佑; ホリエ リョウスケ

タイトル	en Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells
作成者	en Horie, Ryosuke ja 堀江, 亮佑 ja-Kana ホリエ, リョウスケ
アクセス権	open access
権利情報	en Copyright: © Horie et al. https://creativecommons.org/licenses/by-nc-nd/4.0/ en This is an open access article distributed under the terms of Creative Commons Attribution License.
主題	Other en autophagy Other en apoptosis Other en mTOR Other en Spautin-1 Other en osteosarcoma
内容注記	Abstract en Abstract The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway promotes the initiation of autophagy. Although it remains under debate whether chemotherapy-induced autophagy in tumor cells is a protective response or is invoked to promote cell death, recent studies indicate that autophagy is a self-defense mechanism of cancer cells that are subjected to antitumor agents and that blocking autophagy can trigger apoptosis. The aim of this study was to examine the effects of rapamycin, an mTOR inhibitor, on MG63 osteosarcoma cells. We further examined whether the combination of rapamycin and the small molecule inhibitor of autophagy Spautin-1 (specific and potent autophagy inhibitor-1) enhanced the rapamycin-induced apoptosis in MG63 cells. We examined the effects of rapamycin treatment on cell proliferation, phosphorylation of mTOR pathway components, and autophagy by western blot analysis. Furthermore, we examined the effects of rapamycin with or without Spautin-1 on the induction of apoptosis by western blot analysis and immunohistochemical staining. We found that rapamycin inhibited cell proliferation and decreased the phosphorylation of mTOR pathway components in MG63 cells. Rapamycin induced the apoptosis of MG63 cells, and this apoptosis was enhanced by Spautin-1. It was considered that Spautin-1 suppressed the protective mechanism induced by rapamycin in tumor cells and induced apoptosis. Therefore, the combination of an mTOR inhibitor and an autophagy inhibitor may be effective in the treatment of osteosarcoma because it effectively induces the apoptotic pathway.
言語	eng
資源タイプ	doctoral thesis
出版タイプ	P
資源識別子	URI https://kagawa-u.repo.nii.ac.jp/records/377
関連	isVersionOf DOI https://doi.org/10.3892/ijo.2015.3227 isIdenticalTo URI https://dl.ndl.go.jp/pid/11337527 hasVersion URI http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4734606/ PMID 26530936 NAID 500001356526
学位情報	学位授与番号甲第623号学位授与機関識別子名 kakenhi 識別子 16201 機関名称 ja 香川大学 en Kagawa University 学位授与年月日 2016-03-24 学位名 ja 博士（医学）
ファイル	fulltext 本文 1.7 MB (application/pdf) Available2020-11-06 abstract 内容の要旨 68.8 kB (application/pdf) Available2020-11-06 other 審査の結果の要旨 500.9 kB (application/pdf) Available2020-11-06
コンテンツ更新日時	2024-08-24