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  • Title: Trichostatin A, an Inhibitor of Histone Deacetylase, Inhibits the Viability and Invasiveness of Hypoxic Rheumatoid Arthritis Fibroblast-Like Synoviocytes via PI3K/Akt Signaling.
    Author: Zhang Y, Zhang B.
    Journal: J Biochem Mol Toxicol; 2016 Apr; 30(4):163-9. PubMed ID: 26509796.
    Abstract:
    This study was undertaken to explore the effects of trichostatin A (TSA), an inhibitor of histone deacetylase, on the viability, apoptosis, and invasiveness of hypoxic rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs). RA FLSs were exposed to hypoxia for 24 h in the presence or absence of 2 μM TSA and tested for cell viability, apoptosis, invasion, and gene expression. The involvement of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway was checked. TSA significantly inhibited the viability and induced apoptosis of hypoxic RA FLSs, compared to vehicle control. TSA blocked hypoxia-induced invasion of RA FLSs during Matrigel invasion assays and reduced the expression of matrix metalloproteinases (MMP-2 and MMP-9) and PI3K and phosphorylation of Akt. Overexpression of constitutively active Akt reversed TSA-mediated suppression of invasiveness and downregulation of MMP-2 and MMP-9. Our results indicate the antisurvival and antiinvasive activities of TSA in hypoxic RA FLSs, which is associated with inactivation of PI3K/Akt signaling.
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