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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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