Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activation.
Mol Cancer
; 14: 177, 2015 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-26438046
ABSTRACT
BACKGROUND:
Apoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear.METHODS:
We analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo.RESULTS:
Expression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy.CONCLUSIONS:
ASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Autofagia
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Desoxicitidina
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Proteínas Reguladoras de Apoptose
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article