DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth
Braz. j. med. biol. res
;
47(12): 1021-1028, 12/2014. tab, graf
Artículo
en Inglés
| LILACS
| ID: lil-727663
ABSTRACT
DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
S-Adenosilmetionina
/
Neoplasias Gástricas
/
Regulación hacia Abajo
/
Regulación Neoplásica de la Expresión Génica
/
Metilación de ADN
/
Factor C de Crecimiento Endotelial Vascular
/
Antineoplásicos
Límite:
Animales
/
Humanos
/
Masculino
Idioma:
Inglés
Revista:
Braz. j. med. biol. res
Asunto de la revista:
Biologia
/
Medicina
Año:
2014
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
China
Institución/País de afiliación:
Gansu Provincial Hospital/CN
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