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

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28741
Title
Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells
File
Description

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.

(医博甲623)

Author
著者 堀江 亮佑
著者(ヨミ) ホリエ リョウスケ
著者(別表記) Horie Ryosuke
Publication Title
International Journal of Oncology
Publication Title Alternative
Int J Oncol.
Volume
48
Issue
1
Start Page
37
End Page
44
Publisher
Spandidos Publications
Published Date
2015-11-03
ISSN
1019-6439
NCID
AA10992511
PMID
26530936
DOI
10.3892/ijo.2015.3227
Resource Type
Thesis or Dissertation
Language
eng
Relation
PMCID: PMC4734606
Resource URL
https://doi.org/10.3892/ijo.2015.3227
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734606/
Rights
Copyright: © Horie et al.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 License (CC BY-NC-ND 4.0) (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
"This is the Publisher's version of the following article: Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor and an autophagy inhibitor in human osteosarcoma MG63 cells; International Journal of Oncology; Volume 48 Issue 1 (2015) Pages: 37-44; doi:10.3892/ijo.2015.3227, which has been published in final form at https://doi.org/10.3892/ijo.2015.3227 . "
Text Version
ETD
Grant ID
博甲第623号
Grant Date
2016-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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