Schlafen11 Expression Is Associated With the Antitumor Activity of Trabectedin in Human Sarcoma Cell Lines.
Anticancer Res
; 39(7): 3553-3563, 2019 Jul.
Article
em En
| MEDLINE
| ID: mdl-31262879
ABSTRACT
BACKGROUND/AIM:
Trabectedin is a DNA-damaging agent and has been approved for the treatment of patients with advanced soft tissue sarcoma. Schlafen 11 (SLFN11) was identified as a dominant determinant of the response to DNA-damaging agents. The aim of the study was to clarify the association between SLFN11 expression and the antitumor activity of trabectedin. MATERIALS ANDMETHODS:
The antitumor activity of trabectedin was evaluated under different expression levels of SLFN11 regulated by RNA interference and CRISPR-Cas9 systems, and the combined antitumor activity of ataxia telangiectasia and Rad3-related protein kinase (ATR) inhibitor and trabectedin in sarcoma cell lines using in vitro a cell viability assay and in vivo xenograft models.RESULTS:
SLFN11-knockdown cell lines had a lower sensitivity to trabectedin, compared to parental cells. ATR inhibitor enhanced the antitumor activity of trabectedin in SLFN11-knockdown cells and in a SLFN11-knockout xenograft model.CONCLUSION:
SLFN11 expression might be a key factor in the antitumor activity of trabectedin.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
/
Neoplasias de Tecidos Moles
/
Proteínas Nucleares
/
Antineoplásicos Alquilantes
/
Trabectedina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão