STAT3 inhibitor NSC74859 radiosensitizes esophageal cancer via the downregulation of HIF-1α.
Tumour Biol
; 35(10): 9793-9, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24981247
ABSTRACT
Radiotherapy is the main therapy for inoperable and locally advanced esophageal squamous cell carcinoma (ESCC). However, radioresistance in ESCC remains a challenge. The aim of this study is to investigate the radiosensitizing effects of STAT3 inhibitor NSC74859 on ESCC and explore the underlying mechanisms. ECA109 and TE13 cells were exposed to hypoxia, and treated with NSC74859 or radiation, alone or in combination. Cell proliferation, survival, apoptosis, and double-stranded DNA breaks (DSBs) were examined. Nude mice model of ECA109 xenograft was treated with radiation and/or NSC74859. The levels of STAT3, p-STAT3, HIF-1α, and VEGF were detected by Western blot analysis. NSC74859 efficiently radiosensitized ESCC cells and xenografts in nude mice, and inhibited hypoxia-/radiation-induced activation of STAT3 and upregulation of HIF-1α and VEGF expression. NSC74859 confers radiosensitivity in ESCC via the inhibition of STAT3 activation and the downregulation of HIF-1α and VEGF expression. NSC74859 may become a promising radiosensitizer for ESCC radiotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
/
Benzenossulfonatos
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Neoplasias Esofágicas
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Carcinoma de Células Escamosas
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Subunidade alfa do Fator 1 Induzível por Hipóxia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Tumour Biol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China