| Objective:To investigate the influence of histone deacetylase (HDAC) Inhibitor MGCD0103and gemcitabine on the growth of Human osteosarcoma MG-63cells in vitro, and explore the mechanism involved.Methods:Human osteosarcoma MG-63cells were cultured serially and the cells at exponential phase of growth were adopted in experiment. Mono-nuclear cell direct cytotoxicity MTT assay was employed to evaluate the inhibitory effect of MGCD0103(0.01,0.1,1,10,100umol/L) and (or) gemcitabine (0.025,0.05,0.1,0.2,0.4mg/L) on growth of cultured human MG-63osteosarcoma cells. Human osteosarcoma cell lines,MG-63were cultured and treated with different concentration of MGCD0103and gemcitabine in logarithmic growth phase, The cell apoptosis was qualitatively detected by Phase Contrast microscope, Fluorescence microscope respectively。The mRNA expression of HDAC3、MTA1after MGCD0103and gemcitabine treatment was measured by real-time RT-PCR.Western Blotting was used to detect the expressions of Bax、P21,and VEGF.Results:MGCD0103and gemcitabine significantly inhibited the proliferation of bladder cancer cell in a time-and dose-dependent manner (p<0.05). When administered inmoderate or higher concentration,MGCD0103combined with gemcitabine demonstrated synergic effect.After MG-63cells were treated with MGCD0103and gemcitabine,apoptotic cells of typical morphological changes appeared, apoptotic ratio was increased considerably,acetyl level of histone was promoted significantly,and expressions of HDAC3、MTA1、VEGF and Bax、P21were up-regulated or down-regulated respectively.Conclusion:MGCD0103has antitumor effect on osteosarcoma in vitro through inducing cell apoptosis and inhibiting cell proliferation, which might be related to theregulation of acetyl level of histone and expression of genes involved. MGCD0103and gemcitabine is promising to be used as anew antitumor drug to treat osteosarcoma. MGCD0103combined with gemcitabine is promising to be used as a new antitumor method to treat osteosarcoma. |
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