Inhibition of FOXO1mediated autophagy promotes paclitaxelinduced apoptosis of MDAMB231 cells.
Mol Med Rep
; 25(2)2022 02.
Article
em En
| MEDLINE
| ID: mdl-35014689
ABSTRACT
Triplenegative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it often becomes resistant to paclitaxel (PTX) therapy. Autophagy plays an important cytoprotective role in PTXinduced tumor cell death, and targeting autophagy has been promising for improving the efficacy of tumor chemotherapy in recent years. The aim of the present study was to clarify the mechanism of PTX inducing autophagy in TNBC cells to provide a potential clinical chemotherapy strategy of PTX for TNBC. The present study reported that PTX induced both apoptosis and autophagy in MDAMB231 cells and that inhibition of autophagy promoted apoptotic cell death. Furthermore, it was found that forkhead box transcription factor O1 (FOXO1) enhanced PTXinduced autophagy through a transcriptional activation pattern in MDAMB231 cells, which was associated with the downstream target genes autophagy related 5, class III phosphoinositide 3kinase vacuolar protein sorting 34, autophagy related 4B cysteine peptidase, beclin 1 and microtubule associated protein 1 light chain 3ß. Knocking down FOXO1 attenuated the survival of MDAMB231 cells in response to PTX treatment. These findings may be beneficial for improving the treatment efficacy of PTX and to develop autophagic targeted therapy for TNBC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Paclitaxel
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Apoptose
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Neoplasias de Mama Triplo Negativas
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Proteína Forkhead Box O1
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2022
Tipo de documento:
Article