Chelerythrine inhibits the progression of glioblastoma by suppressing the TGFB1-ERK1/2/Smad2/3-Snail/ZEB1 signaling pathway.
Life Sci
; 293: 120358, 2022 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-35092731
ABSTRACT
AIMS:
Glioblastoma (GBM) is the most common and aggressive intracranial tumor with poor prognosis. A large majority of clinical chemotherapeutic agents cannot achieve the desired therapeutic effect. Chelerythrine (CHE), a natural component with multitudinous pharmacological functions, has been proven to have outstanding antitumor effects in addition to antibacterial, anti-inflammatory, and hypotensive effects. However, the anti-GBM effect of CHE has not been reported to date. The purpose of this paper is to observe the anti-GBM effect of CHE and further explore the related mechanism. MATERIALS ANDMETHODS:
GBM cell lines (U251 and T98G) and BALB/c nude mice were used in the experiments. Methyl thiazolyl tetrazolium (MTT) and clone formation assays were applied to detect the viability, proliferation and stemness of GBM cells. Flow cytometry was utilized to identify the effect of CHE on GBM apoptosis. Scratch and Transwell experiments reflected the migration and invasion of cells. In vivo, xenograft tumors were implanted subcutaneously in nude mice. The progression of tumors was assessed by ultrasound and magnetic resonance imaging. Finally, western blot, bioinformatics, and immunohistochemistry experiments were used to explore the molecular mechanisms in depth. KEYFINDINGS:
In vitro tests showed that CHE inhibited the proliferation, stemness, migration, and invasion of GBM cells and induced apoptosis. In vitro, CHE was observed to restrain the progression of xenograft tumors. We eventually proved that the cytotoxicity of CHE was relevant to the TGFB1-ERK1/2/Smad2/3-Snail/ZEB1 signaling pathway.SIGNIFICANCE:
CHE inhibited GBM progression by inhibiting the TGFB1-ERK1/2/Smad2/3-Snail/ZEB1 signaling pathway and is a potential chemotherapeutic drug for GBM.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Glioblastoma
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Proteína Smad2
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Benzofenantridinas
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Fator de Crescimento Transformador beta1
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Homeobox 1 de Ligação a E-box em Dedo de Zinco
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China