Regulation of VEGF gene expression by bisacridine derivative through promoter i-motif for cancer treatment.
Biochim Biophys Acta Gen Subj
; 1868(7): 130631, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38685534
ABSTRACT
BACKGROUND:
Vascular endothelial growth factor (VEGF) is overexpressed in most malignant tumors, which has important impact on tumor angiogenesis and development. Its gene promoter i-motif structure formed by C-rich sequence can regulate gene expression, which is a promising new target for anti-tumor therapy.METHODS:
We screened various compounds and studied their effects on VEGF through extensive experiments, including SPR, MST, TO displacement, FRET, CD, ESI-MS, NMR, MTT, clone formation, qPCR, Western blot, dual-luciferase reporter assay, immunofluorescence, cell scrape, apoptosis, transwell assay, and animal model.RESULTS:
After extensive screening, bisacridine derivative B09 was found to have selective binding and stabilization to VEGF promoter i-motif, which could down-regulate VEGF gene expression. B09 showed potent inhibition on MCF-7 and HGC-27 cell proliferation and metastasis. B09 significantly inhibited tumor growth in xenograft mice model with HGC-27 cells, showing decreased VEGF expression analyzed through immunohistochemistry.CONCLUSION:
B09 could specifically regulate VEGF gene expression, possibly through interacting with promoter i-motif structure. As a lead compound, B09 could be further developed for innovative anti-cancer agent targeting VEGF.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acridinas
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Regulação Neoplásica da Expressão Gênica
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Regiões Promotoras Genéticas
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Fator A de Crescimento do Endotélio Vascular
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta Gen Subj
Ano de publicação:
2024
Tipo de documento:
Article