ID | 62246 |
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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
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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
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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
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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
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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
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Ozaki, Toshifumi
Department of Orthopaedic Surgery, Okayama University Hospital
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Fujiwara, Toshiyoshi
Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | 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. |
Keywords | Osteosarcoma
Chemoresistance
MDR1
Oncolytic adenovirus
p53
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Note | 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
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Published Date | 2021-6-10
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Publication Title |
Cancer Chemotherapy and Pharmacology
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Volume | volume88
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Issue | issue3
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Publisher | Springer Science and Business Media LLC
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Start Page | 513
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End Page | 524
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ISSN | 0344-5704
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NCID | AA00598397
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | author
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PubMed ID | |
DOI | |
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Related Url | isVersionOf https://doi.org/10.1007/s00280-021-04310-5
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Funder Name |
Japan Agency for Medical Research and Development (AMED)
Ministry of Education, Culture, Sports, Science and Technology
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助成番号 | 17ck0106285h001
25293283
16H05416
25293323
25462333
16K10862
15K10446
16K10596
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