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Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models

BACKGROUND: Rivoceranib, a novel tyrosine kinase inhibitor, exhibits anti-tumour effects by selectively blocking vascular endothelial growth factor receptor-2 (VEGFR2) in cancer cells. Recently, the therapeutic effects of rivoceranib on solid tumours have been elucidated in human patients. However,...

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Autores principales: Li, Qiang, Kim, You-Seok, An, Ju-Hyun, Kwon, Jin-Ah, Han, Sang-Hyun, Song, Woo-Jin, Youn, Hwa-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546947/
https://www.ncbi.nlm.nih.gov/pubmed/34702279
http://dx.doi.org/10.1186/s12917-021-03026-1
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author Li, Qiang
Kim, You-Seok
An, Ju-Hyun
Kwon, Jin-Ah
Han, Sang-Hyun
Song, Woo-Jin
Youn, Hwa-Young
author_facet Li, Qiang
Kim, You-Seok
An, Ju-Hyun
Kwon, Jin-Ah
Han, Sang-Hyun
Song, Woo-Jin
Youn, Hwa-Young
author_sort Li, Qiang
collection PubMed
description BACKGROUND: Rivoceranib, a novel tyrosine kinase inhibitor, exhibits anti-tumour effects by selectively blocking vascular endothelial growth factor receptor-2 (VEGFR2) in cancer cells. Recently, the therapeutic effects of rivoceranib on solid tumours have been elucidated in human patients. However, the anti-tumour effects of rivoceranib against canine cancer remain unclear. Here, we investigated the anti-tumour effects of rivoceranib using in vitro and in vivo mouse xenograft models. METHODS: We performed cell proliferation, cell cycle, and migration assays to determine the effects of rivoceranib on canine solid tumour cell lines in vitro. Furthermore, apoptosis and angiogenesis in tumour tissues were examined using a TUNEL assay and immunohistochemistry methods with an anti-cluster of differentiation-31 antibody, respectively. Additionally, the expression levels of cyclin-D1 and VEGFR2 activity were determined using western blot analysis. RESULTS: Rivoceranib treatment showed anti-proliferative effects and mediated cell cycle arrest in the canine melanoma cell line (LMeC) and the mammary gland tumour (MGT) cell line (CHMp). In animal experiments, rivoceranib decreased the average volume of LMeC cells compared to that following control treatment, and similar results were observed in CHMp cells. Histologically, rivoceranib induced apoptosis and exerted an anti-angiogenic effect in tumour tissues. It also downregulated the expression of cyclin-D1 and inhibited VEGFR2 activity. CONCLUSION: Our results show that rivoceranib inhibits proliferation and migration of tumour cells. These findings support the potential application of rivoceranib as a novel chemotherapeutic strategy for canine melanoma and MGTs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-021-03026-1.
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spelling pubmed-85469472021-10-26 Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models Li, Qiang Kim, You-Seok An, Ju-Hyun Kwon, Jin-Ah Han, Sang-Hyun Song, Woo-Jin Youn, Hwa-Young BMC Vet Res Research BACKGROUND: Rivoceranib, a novel tyrosine kinase inhibitor, exhibits anti-tumour effects by selectively blocking vascular endothelial growth factor receptor-2 (VEGFR2) in cancer cells. Recently, the therapeutic effects of rivoceranib on solid tumours have been elucidated in human patients. However, the anti-tumour effects of rivoceranib against canine cancer remain unclear. Here, we investigated the anti-tumour effects of rivoceranib using in vitro and in vivo mouse xenograft models. METHODS: We performed cell proliferation, cell cycle, and migration assays to determine the effects of rivoceranib on canine solid tumour cell lines in vitro. Furthermore, apoptosis and angiogenesis in tumour tissues were examined using a TUNEL assay and immunohistochemistry methods with an anti-cluster of differentiation-31 antibody, respectively. Additionally, the expression levels of cyclin-D1 and VEGFR2 activity were determined using western blot analysis. RESULTS: Rivoceranib treatment showed anti-proliferative effects and mediated cell cycle arrest in the canine melanoma cell line (LMeC) and the mammary gland tumour (MGT) cell line (CHMp). In animal experiments, rivoceranib decreased the average volume of LMeC cells compared to that following control treatment, and similar results were observed in CHMp cells. Histologically, rivoceranib induced apoptosis and exerted an anti-angiogenic effect in tumour tissues. It also downregulated the expression of cyclin-D1 and inhibited VEGFR2 activity. CONCLUSION: Our results show that rivoceranib inhibits proliferation and migration of tumour cells. These findings support the potential application of rivoceranib as a novel chemotherapeutic strategy for canine melanoma and MGTs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-021-03026-1. BioMed Central 2021-10-26 /pmc/articles/PMC8546947/ /pubmed/34702279 http://dx.doi.org/10.1186/s12917-021-03026-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Qiang
Kim, You-Seok
An, Ju-Hyun
Kwon, Jin-Ah
Han, Sang-Hyun
Song, Woo-Jin
Youn, Hwa-Young
Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
title Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
title_full Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
title_fullStr Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
title_full_unstemmed Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
title_short Anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
title_sort anti-tumor effects of rivoceranib against canine melanoma and mammary gland tumour in vitro and in vivo mouse xenograft models
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546947/
https://www.ncbi.nlm.nih.gov/pubmed/34702279
http://dx.doi.org/10.1186/s12917-021-03026-1
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