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ID 62246
著者
Sugiu, Kazuhisa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tazawa, Hiroshi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Hasei, Joe Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamakawa, Yasuaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID
Omori, Toshinori Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Komatsubara, Tadashi Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Mochizuki, Yusuke Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kondo, Hiroya Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID
Osaki, Shuhei Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Fujiwara, Tomohiro Center for Innovative Clinical Medicine, Okayama University Hospital ORCID Kaken ID
Yoshida, Aki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kunisada, Toshiyuki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID researchmap
Ueda, Koji Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research
Urata, Yasuo Oncolys BioPharma, Inc
Kagawa, Shunsuke Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Ozaki, Toshifumi Department of Orthopaedic Surgery, Okayama University Hospital Kaken ID publons researchmap
Fujiwara, Toshiyoshi Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
抄録
Background
Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53–expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells.

Materials and methods
The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model.

Results
DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model.

Conclusion
Our results suggest that MDR1 is attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.
キーワード
Osteosarcoma
Chemoresistance
MDR1
Oncolytic adenovirus
p53
備考
This is a post-peer-review, pre-copyedit version of an article published in Cancer Chemotherapy and Pharmacology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00280-021-04310-5
This fulltext is available in June 2022.
発行日
2021-6-10
出版物タイトル
Cancer Chemotherapy and Pharmacology
出版者
Springer Science and Business Media LLC
ISSN
0344-5704
NCID
AA00598397
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
author
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1007/s00280-021-04310-5
助成機関名
Japan Agency for Medical Research and Development (AMED)
Ministry of Education, Culture, Sports, Science and Technology
助成番号
17ck0106285h001
25293283
16H05416
25293323
25462333
16K10862
15K10446
16K10596