[Inhibitory effect of VPA on multiple myeloma U266 cell proliferation and regulation of histone acetylation].
This study was aimed to investigate the effects of sodium valproate (VPA) on the proliferation and regulation of histone acetylation of multiple myeloma cell line U266. U266 cells were treated with VPA. Cell proliferation was determined by CCK-8 assay, and cell cycle were analyzed by flow cytometry (FCM). The expression level of HDAC1 mRNA was detected by RT-PCR, and the protein levels of HDAC1 and histone H3, H4 acetylation was detected by Western blot. The results showed that the VPA inhibited the proliferation of U266 cells in concentration-and time-dependent manners.After exposure to different concentrations of VPA for 48 hours, the proportion of G(0)/G(1) cells increased, while the proportion of S phase cells decreased. The cell cycle was arrested obviously in G(0)/G(1) phase (p < 0.05). The expression of HDAC1 mRNA was inhibited, and the protein level of HDAC1 was down-regulated, while the histone H3/H4 acetylation was up-regulated in U266 cells. It is concluded that the VPA can inhibit cell proliferation of U266 and induce G(0)/G(1) phase arrest. The increase of histone H3/H4 acetylation resulting from inhibiting HDAC1 by VPA might be considered as a possible mechanism.
Zhu
Yi-Fang
YF
Department of Hematology, The Zhangzhou Municipal Hospital, Fujian Medical University, Zhangzhou 363000, Fujian Province, China.
Ye
Bao-Guo
BG
Shen
Jian-Zhen
JZ
Lin
Cong-Meng
CM
Lin
Fu-An
FA
Shen
Song-Fei
SF
Xu
Cheng-Bo
CB
D000107:Acetylation / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056284:Histone Deacetylase 1 / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D014635:Valproic Acid; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1