Alpha1-antitrypsin protects lung cancer cells from staurosporine-induced apoptosis: the role of bacterial lipopolysaccharide.
Sci Rep
; 10(1): 9563, 2020 06 12.
Article
em En
| MEDLINE
| ID: mdl-32533048
ABSTRACT
Elevated levels of plasma alpha1-antitrypsin (AAT) correlate with a poor prognosis of various cancers. Herein, we investigated effects of exogenous AAT on non-small lung cancer cell lines with high (H1975) and very low (H661) baseline expression of SERPINA1 gene encoding AAT protein. Comparison of cells grown for 3 weeks in a regular medium versus medium supplemented with 2 mg/ml of AAT revealed that in the presence of AAT cells acquire better proliferative properties, resistance to staurosporine (STS)-induced apoptosis, and show higher expression of CLU, a pro-tumorigenic gene coding clusterin protein. Similarly, the co-administration of STS with AAT or addition of AAT to the cells pre-treated with STS abrogated effects of STS in both cell lines. Following experiments with H1975 cells have shown that AAT blocks critical steps in STS-induced cell death inhibition of AKT/MAPK pathways, and activation of caspase 3 and autophagy. AAT does not inhibit apoptosis-triggered by chloroquine (inhibitor of autophagy) or streptonigrin (inducer of p53 pathway). The anti-apoptotic effects of AAT were unaffected by lipopolysaccharide (LPS). However, AAT induced TLR4 levels and enhanced LPS effects on the production of IL-6, a tumor-promoting cytokine. Our data provide further evidence that AAT plays a significant role in the tumorigenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alfa 1-Antitripsina
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Lipopolissacarídeos
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Apoptose
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Resistencia a Medicamentos Antineoplásicos
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Estaurosporina
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Substâncias Protetoras
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article