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  • Title: Arsenic trioxide and promyelocytic leukemia protein-adenovirus synergistically inhibit in vitro and in vivo growth of a hepatoma cell line.
    Author: Cui L, Zhang S, Zhang W, Hu Z, Cao Z, Li T.
    Journal: Oncol Res; 2010; 18(7):305-14. PubMed ID: 20377131.
    Abstract:
    The present study investigated the in vitro and in vivo growth-inhibitory effects of combination therapy with arsenic trioxide (As2O3) and an adenovirus expressing promyelocytic leukemia protein (Ad-PML). Growth of HepG2 cells in culture was not inhibited by As2O3 at concentrations below 5 micromol/L (p > 0.05). However, growth was inhibited by Ad-PML alone and synergistic growth inhibition was observed following combined treatments (p < 0.05). Flow cytometry analyses demonstrated an increase in apoptosis following combined treatment with As2O3 and Ad-PML for 24 h, which was correlated with increased p53 and decreased Bcl-2 expression. To examine treatment effects on in vivo cell growth, control HepG2 cells and cells treated with As2O3, Ad-PML, or both therapies were subcutaneously injected in nude mice. After 6 weeks, tumor volumes were 0.097 +/- 0.031 and 0.083 +/- 0.005 cm3 in the control and As2O3 alone groups, respectively (p > 0.05), but were undetectable in the Ad-PML alone or Ad-PML plus As2O3 groups. Finally, established HepG2 tumors in nude mice were injected with PBS, Ad-PML, As2O3, or Ad-PML plus As2O3, the tumor volumes were measured by ultrasound, and the therapeutic effects were compared. As2O3 alone had no effect at concentrations below 5 micromol/L (p > 0.05), while Ad-PML alone at a multiplicity of infection of 20 or As2O3 plus Ad-PML significantly decreased tumor volumes (p < 0.05). Thus, the combination of As2O3 and Ad-PML has synergistic inhibitory effects on hepatocellular carcinoma (HCC), possibly resulting from regulation of apoptotic gene expression enhanced HCC apoptosis.
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