Abstract

To explore the effects of histone deacetylase inhibitors (HDACIs) on human osteosarcoma in vitro and in vivo. HDACI suberoylanilide hydroxamic acid (SAHA) and sodium butyrate (SB) were employed to examine the effects on human osteosarcoma in vitro and in vivo. The in vitro effects of HDACI SAHA and SB were evaluated in SaOS2 and U2OS human osteosarcoma cell lines. Cell growth, cell cycle progression and histone acetylation were examined by methyl tolyl sulfide (MTS), flow cytometry and Western blot respectively.In addition, SAHA or SB was administered for 4 weeks in a murine xenograph model for assessing the in vitro effects. MTS assay revealed that SAHA and SB significantly suppressed the growth of SaOS2 and U2OS cells in a concentration-dependent manner.Western blot analysis indicated that the levels of acetylated H3 increased after HDACI 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 murine xenograph model with SaOS2 was inhibited by SAHA and SB compared with vehicle control. HDACI SAHA and SB significantly inhibit the growth of human osteosarcoma cells and induce cell cycle arrest. Meanwhile, the tumor inhibitory effects were also validated in a murine xenograft model.

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