title: [Valproic Acid Represses Autophagy and Enhances the Anti-myeloma Activity of DNA-damaging Drugs].
abstract: OBJECTIVE
  To explore the effect of valproic acid(VPA) on anti-myeloma activity of Doxorubicin(DOX) or Melphalan(MEL) and its related mechanism.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Jin
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Bao-Xia
authors.initials: BX
authors.lastname: Dong
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Tang
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China.
authors.forename: Guang-Xun
authors.initials: GX
authors.lastname: Gao
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. E-mail: guht3360@fmmu.edu.cn.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Gu
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. E-mail: 13709220311@126.com.
authors.forename: Mi-Mi
authors.initials: MM
authors.lastname: Shu
authors.affiliation: Department of Hematology, Xijing Hospital, The Fourth Military Medical University, Hematologic disease Center of Chinese People's Liberation Army, Xi'an 710032, Shaanxi Province, China. E-mail: xiequnchen@fmmu.edu.cn.
authors.forename: Xie-Qun
authors.initials: XQ
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA; D004249:DNA Damage; D004317:Doxorubicin; D006801:Humans; D009101:Multiple Myeloma; D014635:Valproic Acid
chemical_list: D014635:Valproic Acid; D004317:Doxorubicin; D004247:DNA