THYMOSIN-ALPHA(1), BUT NOT INTERFERON-ALPHA, SPECIFICALLY INHIBITS ANCHORAGE-INDEPENDENT GROWTH OF HEPATITIS-B VIRAL TRANSFECTED HEPG2 CELLS

Background: Thymosin-alpha(1) is a biological response modifier that h as been used clinically, alone and in combination with interferon-alph a for the treatment of chronic hepatitis B viral infection, Both immun omodulatory and immediate intracellular mechanisms have been postulate d to explain the effect of these two agents on HBV-infected hepatocyte s, Methods: In this study, hepatitis B transfected HepG2 hepatoblastom a cells (HepG2-Nu2), derived from 2.2.15 cells, were used as an in vit ro model to determine the efficacy of thymosin-alpha(1) and interferon -alpha, individually and combined, as proliferation inhibitors of HBV- infected cells, For comparison, parental HepG2 cells and an SV40-trans fected HepG2 cell line (HepG2P9T2) were also evaluated, Results: In a clonogenic soft agar assay, thymosin-alpha(1) inhibited the anchorage- independent growth of the HepG2-Nu2 cells by 40% compared with untreat ed controls, but did not inhibit parental HepG2 or HepG2P9T2 clonal gr owth, The response was dose dependent over concentrations spanning thr ee log units, In comparison, 10000 units/ml of interferon-alpha inhibi ted parental HepG2, HepG2-N4Z and HepG2P9T2 by 33%, 41% and 87%, respe ctively, The combination of thymosin-alpha(1) and interferon-a consist ently inhibited HepG2-Nu2 clonal growth more effectively than either t reatment alone, reaching maximum inhibition levels of 51%. Conclusions : Thymosin-alpha(1) specifically inhibits the tumorigenic growth of HB V-transfected HepG2 cells in contrast to the general inhibition displa yed by interferon-alpha. This panel of cell lines may be an important resource for dissecting the mechanism by which thymosin, alone or in c ombination with other drugs, influences HBV-infected hepatocytes and/o r HBV-associated carcinoma.