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Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression
Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061981/ https://www.ncbi.nlm.nih.gov/pubmed/33886686 http://dx.doi.org/10.1371/journal.pone.0250643 |
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author | Omori, Toshinori Tazawa, Hiroshi Yamakawa, Yasuaki Osaki, Shuhei Hasei, Joe Sugiu, Kazuhisa Komatsubara, Tadashi Fujiwara, Tomohiro Yoshida, Aki Kunisada, Toshiyuki Urata, Yasuo Kagawa, Shunsuke Ozaki, Toshifumi Fujiwara, Toshiyoshi |
author_facet | Omori, Toshinori Tazawa, Hiroshi Yamakawa, Yasuaki Osaki, Shuhei Hasei, Joe Sugiu, Kazuhisa Komatsubara, Tadashi Fujiwara, Tomohiro Yoshida, Aki Kunisada, Toshiyuki Urata, Yasuo Kagawa, Shunsuke Ozaki, Toshifumi Fujiwara, Toshiyoshi |
author_sort | Omori, Toshinori |
collection | PubMed |
description | Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS. |
format | Online Article Text |
id | pubmed-8061981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80619812021-05-04 Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression Omori, Toshinori Tazawa, Hiroshi Yamakawa, Yasuaki Osaki, Shuhei Hasei, Joe Sugiu, Kazuhisa Komatsubara, Tadashi Fujiwara, Tomohiro Yoshida, Aki Kunisada, Toshiyuki Urata, Yasuo Kagawa, Shunsuke Ozaki, Toshifumi Fujiwara, Toshiyoshi PLoS One Research Article Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS. Public Library of Science 2021-04-22 /pmc/articles/PMC8061981/ /pubmed/33886686 http://dx.doi.org/10.1371/journal.pone.0250643 Text en © 2021 Omori et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Omori, Toshinori Tazawa, Hiroshi Yamakawa, Yasuaki Osaki, Shuhei Hasei, Joe Sugiu, Kazuhisa Komatsubara, Tadashi Fujiwara, Tomohiro Yoshida, Aki Kunisada, Toshiyuki Urata, Yasuo Kagawa, Shunsuke Ozaki, Toshifumi Fujiwara, Toshiyoshi Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression |
title | Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression |
title_full | Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression |
title_fullStr | Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression |
title_full_unstemmed | Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression |
title_short | Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression |
title_sort | oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic mcl1 expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061981/ https://www.ncbi.nlm.nih.gov/pubmed/33886686 http://dx.doi.org/10.1371/journal.pone.0250643 |
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