title: Histone deacetylase inhibitors suppress the growth of human osteosarcomas in vitro and in vivo.
abstract: OBJECTIVE
  Although the antitumor efficacy of histone deacetylase inhibitors (HDACIs) has been referred to as a promising new treatment strategy in malignancies, how they exert their effects on human osteosarcoma in vitro and in vivo is yet not well understood. In this study, we employed HDACIs suberoylanilide hydroxamic acid (SAHA) and sodium butyrate (SB) to investigate their effects on human osteosarcoma in vitro and in vivo.
  
  
  METHODS
  The in vitro effects of HDACIs SAHA and SB were evaluated in SaOS2 and U2OS human osteosarcoma cell lines. Cell growth, cell cycle progression and histone acetylation were investigated by MTS, flow cytometry and western blotting, respectively. In addition, SAHA or SB was administered for 4 weeks in mice xenograph models for assessing the in vivo effects.
  
  
  RESULTS
  MTS assays revealed that SAHA and SB significantly suppressed the growth of SaOS2 and U2OS cells in a concentration-dependent manner. Western blotting analysis indicated that the levels of acetylated H3 were increased after HDACIs treatment. Flow cytometry showed that SAHA arrested the cell cycle in G1 and G2/M phase, while SB arrested the cell cycle in G2/M phase. The tumor growth of mice xenograph models with SaOS2 was inhibited by SAHA and SB compared with vehicle control.
  
  
  CONCLUSIONS
  HDACIs SAHA and SB significantly inhibit the growth of human osteosarcoma cells and induce cell cycle arrest. The tumor inhibitory effects were also validated in mice xenograft models.
authors.affiliation: Department of Pediatric Orthopaedics, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhenkai
authors.initials: Z
authors.lastname: Wu
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Zhi
authors.initials: Z
authors.lastname: Shan
authors.forename: Yaping
authors.initials: Y
authors.lastname: Ju
authors.forename: Siyu
authors.initials: S
authors.lastname: Li
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020148:Butyric Acid / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D020148:Butyric Acid; D000077337:Vorinostat