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YM155 enhances the cytotoxic activity of etoposide against canine osteosarcoma cells
Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to dete...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Japanese Society of Veterinary Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715925/ https://www.ncbi.nlm.nih.gov/pubmed/31308291 http://dx.doi.org/10.1292/jvms.19-0029 |
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author | ONG, Siew Mei SAEKI, Kohei KOK, Mun Keong NAKAGAWA, Takayuki NISHIMURA, Ryohei |
author_facet | ONG, Siew Mei SAEKI, Kohei KOK, Mun Keong NAKAGAWA, Takayuki NISHIMURA, Ryohei |
author_sort | ONG, Siew Mei |
collection | PubMed |
description | Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to determine if YM155, a small-molecule survivin inhibitor, potentiates the chemotherapeutic efficacy of etoposide against canine OSA in vitro and in vivo. In cell culture, YM155 enhanced the cytotoxic effect of etoposide against canine OSA cell lines; however, the molecular mechanism behind this effect was heterogeneous, as only one cell line had an elevated apoptotic level. In addition, this effect was not associated with survivin suppression in two of the cell lines. These results suggest that the molecular target of YM155 is not restricted to survivin alone. When tested on a murine xenograft model, the average tumor volume of the combination treatment group (YM155, 5 mg/kg, intraperitoneally, 5 consecutive days/week; and etoposide, 20 mg/kg, intraperitoneally, every 5 days) was 66% smaller than the control group, although this difference was not statistically significant (P=0.17). Further studies to improve the treatment protocol are necessary to confirm the findings of this study. |
format | Online Article Text |
id | pubmed-6715925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The Japanese Society of Veterinary Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-67159252019-09-06 YM155 enhances the cytotoxic activity of etoposide against canine osteosarcoma cells ONG, Siew Mei SAEKI, Kohei KOK, Mun Keong NAKAGAWA, Takayuki NISHIMURA, Ryohei J Vet Med Sci Laboratory Animal Science Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to determine if YM155, a small-molecule survivin inhibitor, potentiates the chemotherapeutic efficacy of etoposide against canine OSA in vitro and in vivo. In cell culture, YM155 enhanced the cytotoxic effect of etoposide against canine OSA cell lines; however, the molecular mechanism behind this effect was heterogeneous, as only one cell line had an elevated apoptotic level. In addition, this effect was not associated with survivin suppression in two of the cell lines. These results suggest that the molecular target of YM155 is not restricted to survivin alone. When tested on a murine xenograft model, the average tumor volume of the combination treatment group (YM155, 5 mg/kg, intraperitoneally, 5 consecutive days/week; and etoposide, 20 mg/kg, intraperitoneally, every 5 days) was 66% smaller than the control group, although this difference was not statistically significant (P=0.17). Further studies to improve the treatment protocol are necessary to confirm the findings of this study. The Japanese Society of Veterinary Science 2019-07-15 2019-08 /pmc/articles/PMC6715925/ /pubmed/31308291 http://dx.doi.org/10.1292/jvms.19-0029 Text en ©2019 The Japanese Society of Veterinary Science This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Laboratory Animal Science ONG, Siew Mei SAEKI, Kohei KOK, Mun Keong NAKAGAWA, Takayuki NISHIMURA, Ryohei YM155 enhances the cytotoxic activity of etoposide against canine osteosarcoma cells |
title | YM155 enhances the cytotoxic activity of etoposide against canine
osteosarcoma cells |
title_full | YM155 enhances the cytotoxic activity of etoposide against canine
osteosarcoma cells |
title_fullStr | YM155 enhances the cytotoxic activity of etoposide against canine
osteosarcoma cells |
title_full_unstemmed | YM155 enhances the cytotoxic activity of etoposide against canine
osteosarcoma cells |
title_short | YM155 enhances the cytotoxic activity of etoposide against canine
osteosarcoma cells |
title_sort | ym155 enhances the cytotoxic activity of etoposide against canine
osteosarcoma cells |
topic | Laboratory Animal Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715925/ https://www.ncbi.nlm.nih.gov/pubmed/31308291 http://dx.doi.org/10.1292/jvms.19-0029 |
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