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Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation

Although many cancer patients are administered radiotherapy for their treatment, the interaction between tumor cells and macrophages in the tumor microenvironment attenuates the curative effects of radiotherapy. The enhanced activation of mTOR signaling in the tumors promotes tumor radioresistance....

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Autores principales: Woo, Yunseo, Lee, Hyo-Ji, Kim, Jeongyeon, Kang, Seung Goo, Moon, Sungjin, Han, Jeong A., Jung, Young Mee, Jung, Yu-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093631/
https://www.ncbi.nlm.nih.gov/pubmed/33959512
http://dx.doi.org/10.3389/fonc.2021.665420
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author Woo, Yunseo
Lee, Hyo-Ji
Kim, Jeongyeon
Kang, Seung Goo
Moon, Sungjin
Han, Jeong A.
Jung, Young Mee
Jung, Yu-Jin
author_facet Woo, Yunseo
Lee, Hyo-Ji
Kim, Jeongyeon
Kang, Seung Goo
Moon, Sungjin
Han, Jeong A.
Jung, Young Mee
Jung, Yu-Jin
author_sort Woo, Yunseo
collection PubMed
description Although many cancer patients are administered radiotherapy for their treatment, the interaction between tumor cells and macrophages in the tumor microenvironment attenuates the curative effects of radiotherapy. The enhanced activation of mTOR signaling in the tumors promotes tumor radioresistance. In this study, the effects of rapamycin on the interaction between tumor cells and macrophages were investigated. Rapamycin and 3BDO were used to regulate the mTOR pathway. In vitro, tumor cells cocultured with macrophages in the presence of each drug under normoxic or hypoxic conditions were irradiated with γ–rays. In vivo, mice were irradiated with γ–radiation after injection with DMSO, rapamycin and 3BDO into tumoral regions. Rapamycin reduced the secretion of IL-4 in tumor cells as well as YM1 in macrophages. Mouse recombinant YM1 decreased the enhanced level of ROS and the colocalized proportion of both xCT and EEA1 in irradiated tumor cells. Human recombinant YKL39 also induced results similar to those of YM1. Moreover, the colocalized proportion of both xCT and LC3 in tumor tissues was elevated by the injection of rapamycin into tumoral regions. Overall, the suppression of mTOR signaling in the tumor microenvironment might be useful for the improvement of tumor radioresistance.
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spelling pubmed-80936312021-05-05 Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation Woo, Yunseo Lee, Hyo-Ji Kim, Jeongyeon Kang, Seung Goo Moon, Sungjin Han, Jeong A. Jung, Young Mee Jung, Yu-Jin Front Oncol Oncology Although many cancer patients are administered radiotherapy for their treatment, the interaction between tumor cells and macrophages in the tumor microenvironment attenuates the curative effects of radiotherapy. The enhanced activation of mTOR signaling in the tumors promotes tumor radioresistance. In this study, the effects of rapamycin on the interaction between tumor cells and macrophages were investigated. Rapamycin and 3BDO were used to regulate the mTOR pathway. In vitro, tumor cells cocultured with macrophages in the presence of each drug under normoxic or hypoxic conditions were irradiated with γ–rays. In vivo, mice were irradiated with γ–radiation after injection with DMSO, rapamycin and 3BDO into tumoral regions. Rapamycin reduced the secretion of IL-4 in tumor cells as well as YM1 in macrophages. Mouse recombinant YM1 decreased the enhanced level of ROS and the colocalized proportion of both xCT and EEA1 in irradiated tumor cells. Human recombinant YKL39 also induced results similar to those of YM1. Moreover, the colocalized proportion of both xCT and LC3 in tumor tissues was elevated by the injection of rapamycin into tumoral regions. Overall, the suppression of mTOR signaling in the tumor microenvironment might be useful for the improvement of tumor radioresistance. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8093631/ /pubmed/33959512 http://dx.doi.org/10.3389/fonc.2021.665420 Text en Copyright © 2021 Woo, Lee, Kim, Kang, Moon, Han, Jung and Jung https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Woo, Yunseo
Lee, Hyo-Ji
Kim, Jeongyeon
Kang, Seung Goo
Moon, Sungjin
Han, Jeong A.
Jung, Young Mee
Jung, Yu-Jin
Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation
title Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation
title_full Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation
title_fullStr Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation
title_full_unstemmed Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation
title_short Rapamycin Promotes ROS-Mediated Cell Death via Functional Inhibition of xCT Expression in Melanoma Under γ-Irradiation
title_sort rapamycin promotes ros-mediated cell death via functional inhibition of xct expression in melanoma under γ-irradiation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093631/
https://www.ncbi.nlm.nih.gov/pubmed/33959512
http://dx.doi.org/10.3389/fonc.2021.665420
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