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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0250643 |
| _version_ | 1818891732194951168 |
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| author | Toshinori Omori Hiroshi Tazawa Yasuaki Yamakawa Shuhei Osaki Joe Hasei Kazuhisa Sugiu Tadashi Komatsubara Tomohiro Fujiwara Aki Yoshida Toshiyuki Kunisada Yasuo Urata Shunsuke Kagawa Toshifumi Ozaki Toshiyoshi Fujiwara |
| author_facet | Toshinori Omori Hiroshi Tazawa Yasuaki Yamakawa Shuhei Osaki Joe Hasei Kazuhisa Sugiu Tadashi Komatsubara Tomohiro Fujiwara Aki Yoshida Toshiyuki Kunisada Yasuo Urata Shunsuke Kagawa Toshifumi Ozaki Toshiyoshi Fujiwara |
| author_sort | Toshinori Omori |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T17:45:29Z |
| format | Article |
| id | doaj.art-aa5ad1fb44474459ae6369bdf391f6a2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T17:45:29Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aa5ad1fb44474459ae6369bdf391f6a22022-12-21T20:12:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01164e025064310.1371/journal.pone.0250643Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression.Toshinori OmoriHiroshi TazawaYasuaki YamakawaShuhei OsakiJoe HaseiKazuhisa SugiuTadashi KomatsubaraTomohiro FujiwaraAki YoshidaToshiyuki KunisadaYasuo UrataShunsuke KagawaToshifumi OzakiToshiyoshi FujiwaraSoft 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.https://doi.org/10.1371/journal.pone.0250643 |
| spellingShingle | Toshinori Omori Hiroshi Tazawa Yasuaki Yamakawa Shuhei Osaki Joe Hasei Kazuhisa Sugiu Tadashi Komatsubara Tomohiro Fujiwara Aki Yoshida Toshiyuki Kunisada Yasuo Urata Shunsuke Kagawa Toshifumi Ozaki Toshiyoshi Fujiwara Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0250643 |
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