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
Dans Chinois
| WPRIM
| ID: wpr-357284
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>
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Acétylation
/
Autophagie
/
Altération de l'ADN
/
ADN
/
Doxorubicine
/
Acide valproïque
/
Lignée cellulaire tumorale
/
Prolifération cellulaire
/
Myélome multiple
Limites du sujet:
Humains
langue:
Chinois
Texte intégral:
Journal of Experimental Hematology
Année:
2015
Type:
Article
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS