| Objective:Aberrant DNA acetylation is associated with carcinogenesis. The antitumor effects of histon deacetylase inhibitors are now under intensive investigation. In this study, the effects of histone deacetylase inhititor trichostatin A (TSA) on the proliferation and apotosis of different hepatoma cell lines and on Hepatitis B virus (HBV) replication were investigated. TSA has been shown to induce the expression of MHC II,CD40 and B7-1/2 and enhance antitumor immunoresponse, MICA/B is the ligand of NKG2D receptor ,the engagement of NKG2D is a sufficient stimulus to activate cytolysis by NK cells. Therefore, the effect of TSA on the expression of MICA/B was also invesitgated.Methods:Human hepatoma cell lines HepG2, HepG2.2.15, QGY7701 and normal liver cell line L02 were treated with TSA, the effects on proliferation and apoptosis were examined by MTT assay and agarose gel electrophoresis of DNA; the expression of MICA/B was analyzed by real time RT-PCR, immunofluorescence and flow cytometry. Hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) in culture medium were measured using the Abbott Microparticle Enzyme Immunoassay kits; The medium HBV DNA was quantified using HBV real-time PCR kit.Results:(a)Treatment with TSA resulted in growth repression and apoptosis in hepatoma cell lines, however, the normal liver cell line L02 was not sensitive to TSA treatment. (b) TSA induced MICA/B expression in hepatoma cell lines.(c)TSA treatment enhanced Hepatitis B virus(HBV) replication.Conlusion:TSA treatment could inhibit proliferation of different hepatoma lines, and the normal liver cell line L02 is not sensitive to TSA treatment. TSA induces the expression of MICA/B in hepatocellular carcinoma cells. However, TSA stimulates HBV replication. Therefore, our results suggest that TSA might be a good chemotherapic candidate for hepatocellular carcinoma patients without HBV infection but may not be suited to treat hepatocellular cancer patients with HBV infection. |
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