TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy
The anticancer effects of Src kinase inhibitors are controversial. This study found an association between alterations in the TP53 gene and the synergy score for combination treatment with doxorubicin and an Src kinase inhibitor using human osteosarcoma cell lines (MG63 and U2OS) and human colon can...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-08-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428318794217 |
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| author | Yun Sun Lee Ji-Yoon Choi Jeeyun Lee Da Mi Shim Jaesoo Kim Woong-Yang Park Do-Hyun Nam Sung Wook Seo |
| author_facet | Yun Sun Lee Ji-Yoon Choi Jeeyun Lee Da Mi Shim Jaesoo Kim Woong-Yang Park Do-Hyun Nam Sung Wook Seo |
| author_sort | Yun Sun Lee |
| collection | DOAJ |
| description | The anticancer effects of Src kinase inhibitors are controversial. This study found an association between alterations in the TP53 gene and the synergy score for combination treatment with doxorubicin and an Src kinase inhibitor using human osteosarcoma cell lines (MG63 and U2OS) and human colon cancer cell line. Doxorubicin was found to activate signal transducer and activator of transcription 3 via Src kinase in cancer cells harboring alterations in TP53. A drug combination study using patient-derived cells confirmed that an Src kinase inhibitor synergizes with doxorubicin in cancer cells harboring alterations in TP53, while antagonizing its effect in cancer cells expressing wild-type TP53. Our findings suggest that genetic alterations in TP53 are a critical factor in determining the use of a combination treatment of doxorubicin and Src inhibitors. |
| format | Article |
| id | doaj-art-c0149f8e8a7e42c898a00674d088c9b5 |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2018-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-c0149f8e8a7e42c898a00674d088c9b52025-08-20T02:51:35ZengSAGE PublishingTumor Biology1423-03802018-08-014010.1177/1010428318794217TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapyYun Sun Lee0Ji-Yoon Choi1Jeeyun Lee2Da Mi Shim3Jaesoo Kim4Woong-Yang Park5Do-Hyun Nam6Sung Wook Seo7Department of Orthopaedic Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaDepartment of Orthopaedic Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaDepartment of Medicine, Division of Hematology and Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaDepartment of Orthopaedic Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaDepartment of Orthopaedic Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaSamsung Genome Institute, Samsung Medical Center, Seoul, KoreaDepartment of Neurosurgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaDepartment of Orthopaedic Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, KoreaThe anticancer effects of Src kinase inhibitors are controversial. This study found an association between alterations in the TP53 gene and the synergy score for combination treatment with doxorubicin and an Src kinase inhibitor using human osteosarcoma cell lines (MG63 and U2OS) and human colon cancer cell line. Doxorubicin was found to activate signal transducer and activator of transcription 3 via Src kinase in cancer cells harboring alterations in TP53. A drug combination study using patient-derived cells confirmed that an Src kinase inhibitor synergizes with doxorubicin in cancer cells harboring alterations in TP53, while antagonizing its effect in cancer cells expressing wild-type TP53. Our findings suggest that genetic alterations in TP53 are a critical factor in determining the use of a combination treatment of doxorubicin and Src inhibitors.https://doi.org/10.1177/1010428318794217 |
| spellingShingle | Yun Sun Lee Ji-Yoon Choi Jeeyun Lee Da Mi Shim Jaesoo Kim Woong-Yang Park Do-Hyun Nam Sung Wook Seo TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy Tumor Biology |
| title | TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy |
| title_full | TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy |
| title_fullStr | TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy |
| title_full_unstemmed | TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy |
| title_short | TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy |
| title_sort | tp53 dependence on the effect of doxorubicin and src inhibitor combination therapy |
| url | https://doi.org/10.1177/1010428318794217 |
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