The effect of HIF-1α inhibition in breast cancer cells prior to doxorubicin treatment under conditions of normoxia and hypoxia.
Exp Cell Res
; 419(2): 113334, 2022 10 15.
Article
em En
| MEDLINE
| ID: mdl-36044939
ABSTRACT
BACKGROUND:
Oxygen deprivation is a key hallmark within solid tumours that contributes to breast-tumour pathophysiology. Under these conditions, neoplastic cells activate several genes, regulated by the HIF-1 transcription factor, which alters the tumour microenvironment to promote survival - including resistance to cell death in therapeutic attempts such as doxorubicin (Dox) treatment.METHODS:
We investigated HIF-1É as a therapeutic target to sensitize breast cancer cells to Dox treatment. Under both normoxic (21% O2) and hypoxic (â¼0.1% O2) conditions, the HIF-1 inhibitor, 2-methoxyestradiol (2-ME), was investigated as an adjuvant for its ability to alter MCF-7 cell viability, apoptosis, autophagy and molecular pathways which are often associated with increased cell survival.RESULTS:
Here we observed that an inverse relationship between HIF-1É and apoptosis exists and that Dox promotes autophagy under hypoxic conditions. Although adjuvant therapy with 2-ME induced an antagonistic effect in breast cancer cells, upregulated HIF-1É expression in a hypoxic environment promotes treatment resistance and this was attenuated once HIF-1É gene expression was silenced.CONCLUSION:
Therefore, highlighting the identification of possible hypoxia-targeting therapies for breast cancer patients can be beneficial by promoting more favourable treatment responses.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2022
Tipo de documento:
Article