Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway.
Oncol Rep
; 46(3)2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-34296295
ABSTRACT
High malignancy and high mortality of glioma render it urgent to elucidate the underlying mechanisms of glioma carcinogenesis and explore novel targets for therapy. Epidemiologic and clinical studies have revealed that chronic stress promotes the progression of various solid tumors and is correlated with poor prognosis; however, findings reporting the involvement of chronic stress in glioma are rare. In the present study, a chronic restraint animal model and a chronic stress cell model were established to explore the effects of chronic stress on glioma and its molecular mechanisms. The results revealed that chronic stress promoted glioma growth in vivo, and the serum levels of the stress hormones glucocorticoid (GC) and noradrenaline (NE) were significantly increased. In addition, GC and NE were verified to accelerate the proliferation of glioma cells in vitro. Mechanistically, the phosphatidylinositol 3kinase (PI3K)/Akt signaling pathway was revealed to be activated under stress conditions, and inhibition of the expression of pAkt could restrain the stress hormoneinduced glioma cell proliferation. In addition, our data indicated that the GC receptor (GR) and ßadrenergic receptors (ADRBs) were both required for the biological functions of GC and NE in glioma cells. In conclusion, these results indicated that chronic stress and the stress hormones GC and NE activated PI3K/Akt signaling through binding to GR and ADRBs, thereby promoting glioma cell growth. Our findings may provide potential therapeutic targets and pave the way for the development of new strategies to protect patients with glioma from the detrimental effects of stress on tumor progression.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Regulação Neoplásica da Expressão Gênica
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Fosfatidilinositol 3-Quinases
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Proteínas Proto-Oncogênicas c-akt
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Glioma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article