Upregulation of GRIM-19 augments the sensitivity of prostate cancer cells to docetaxel by targeting Rad23b.
Clin Exp Pharmacol Physiol
; 47(1): 76-84, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31531888
ABSTRACT
The gene associated with retinoid-interferon mortality (GRIM-19) has been reported to be correlated with drug resistance, whereas its functional role in prostate cancer (PC) is not fully understood. This study aims to clarify the potential role and molecular mechanisms of GRIM-19 on the response of PC cells to chemical drug docetaxel. mRNA and protein level of GRIM-19 expression in cells and tissues of PC were measured by quantitative real-time PCR and western blot, respectively. Knock-down of GRIM-19 in PC cells was performed using siRNA. Cell apoptosis was determined by flow cytometric analysis. DNA damage in PC cells was detected by γ-H2AX staining. GRIM-19 was downregulated in PC tissues and cell lines. Knock-down of GRIM-19 increased the resistance of PC cells to docetaxel, and overexpression of GRIM-19 promoted docetaxel-induced apoptotic death in PC cells. Mechanistically, GRIM-19 downregulated the expression of the survival gene Rad23b, which promoted DNA damage repair. Overexpression of Rad23b reversed GRIM-19-mediated response to docetaxel in PC cells. GRIM-19 promoted the sensitivity of PC cells to docetaxel by downregulating Rad23b, which may serve as a promising target to develop a better strategy of chemotherapy for PC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Prostata
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Regulação para Cima
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Enzimas Reparadoras do DNA
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Proteínas de Ligação a DNA
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Proteínas Reguladoras de Apoptose
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Docetaxel
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NADH NADPH Oxirredutases
Tipo de estudo:
Diagnostic_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China