Valproic Acid Represses Autophagy and Enhances the Anti-myeloma Activity of DNA-damaging Drugs / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 718-721, 2015.
Article
em Zh
| WPRIM
| ID: wpr-357284
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of valproic acid(VPA) on anti-myeloma activity of Doxorubicin(DOX) or Melphalan(MEL) and its related mechanism.</p><p><b>METHODS</b>Human multiple myeloma(MM) cells were treated with VPA of non-toxic dose in absence and presence of DOX or MEL at different concentrations (ie. IC10, IC20, IC40). The cell proliferation was detected by MTT method. Western blot was used to detect the expression levels of autophagy-related proteins (LC3, ATG5, ATG7) and acetylated histone H4K16ac.</p><p><b>RESULTS</b>Cell proliferation inhibition markedly increased in VPA plus DOX or MEL as compared with DOX or MEL alone (P<0.05). Both LC3 and H4K16ac expression levels in co-treatment were between VPA and DOX or MEL treated alone. Importantly, VPA of non-toxic dose not only augmented the anti-myeloma activity of DOX or MEL, but also down-regulated the autophagy-related protein expression and increases H4K16ac protein levels.</p><p><b>CONCLUSION</b>H4K16ac can inhibit the transcription of autophagy-related genes, The VPA enhance the anti-myeloma activity of DNA-damaging drugs, at least in part, via H4K16ac-mediated suppression of cytoprotective autophagy.</p>
Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Acetilação
/
Autofagia
/
Dano ao DNA
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DNA
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Doxorrubicina
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Ácido Valproico
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Linhagem Celular Tumoral
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Proliferação de Células
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Mieloma Múltiplo
Limite:
Humans
Idioma:
Zh
Revista:
Journal of Experimental Hematology
Ano de publicação:
2015
Tipo de documento:
Article