Norcantharidin inhibits proliferation and promotes apoptosis via c-Met/Akt/mTOR pathway in human osteosarcoma cells.
Cancer Sci
; 110(2): 582-595, 2019 Feb.
Article
em En
| MEDLINE
| ID: mdl-30520540
ABSTRACT
Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. The aim of the present study was to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppress the migration and invasion, decrease the colony-forming ability and induce S phase cell cycle arrest of OS cells in a dose-dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum stress and c-Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These results provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteossarcoma
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Apoptose
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Compostos Bicíclicos Heterocíclicos com Pontes
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Proteínas Proto-Oncogênicas c-met
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Proliferação de Células
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article