Reversine suppresses osteosarcoma cell growth through targeting BMP-Smad1/5/8-mediated angiogenesis.
Microvasc Res
; 135: 104136, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33450295
ABSTRACT
Reversine, or 2-(4-morpholinoanilino)-6cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule exhibits tumor-suppressive activities through different molecular mechanisms. In this study, in vitro and in vivo angiogenic models were used to elucidate the effect of Reversine on angiogenesis in the tumor suppression. Firstly, we grafted osteosarcoma-derived MNNG/HOS cell aggregates onto chick embryonic chorioallantoic membrane (CAM) to examine the vascularization of these grafts following Reversine treatment. Following culture, it was determined that Reversine inhibited MNNG/HOS grafts growth, and decreased the density of blood vessels in the chick CAM. We then used CAM and chick embryonic yolk-sac membrane (YSM) to investigate the effects of Reversine on angiogenesis. The results revealed Reversine inhibited the proliferation of endothelial cells, where cells were mainly arrested at G1/S phase of the cell cycle. Scratch-wound assay with HUVECs revealed that Reversine suppressed cell migration in vitro. Furthermore, endothelial cells tube formation assay and chick aortic arch sprouting assay demonstrated Reversine inhibited the sprouting, migration of endothelial cells. Lastly, qPCR and western blot analyses showed BMP-associated Smad1/5/8 signaling expressions were up-regulated by Reversine treatment. Our results showed that Reversine could suppress tumor growth by inhibiting angiogenesis through BMP signaling, and suggests a potential use of Reversine as an anti-tumor therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Purinas
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Neoplasias Ósseas
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Osteossarcoma
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Morfolinas
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Neovascularização Fisiológica
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Proteínas Morfogenéticas Ósseas
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Inibidores da Angiogênese
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Proliferação de Células
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Proteínas Smad
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Células Endoteliais da Veia Umbilical Humana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Microvasc Res
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China