Thymosin-α 1, but not interferon-α, specifically inhibits anchorage-independent growth of hepatitis B viral transfected HepG2 cells

• Published in: Journal of hepatology 1996-12, Vol.25 (6), p.814-820
• Main Authors: Moshier, Jeffrey A., Mutchnick, Milton G., Dosescu, Julie, Holtz, Todd K., Akkary, Sami, Mahakala, Kavita, Merline, Joseph R., Naylor, Paul H.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Cell Division - drug effects; Cell Transformation, Viral; Clonogenic growth; DNA, Viral - biosynthesis; DNA, Viral - drug effects; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatoblastoma - drug therapy; Hepatoblastoma - virology; Humans; Interferon-alpha - administration & dosage; Interferon-alpha - pharmacology; Liver Neoplasms - drug therapy; Liver Neoplasms - virology; Thymalfasin; Thymosin - administration & dosage; Thymosin - analogs & derivatives; Thymosin - pharmacology; Thymosin-α 1; Transfection; Tumor Cells, Cultured; Tumorigenicity; Virus Replication - drug effects
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(96)80283-2

Background: Thymosin-α 1 is a biological response modifier that has been used clinically, alone and in combination with interferon-α for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracelluilar mechanisms have been postulated to explain the effect of these two agents on HBV-infected hepatocytes. Methods: In this study, hepatitis B transfected HepG2 hepatoblastoma cells (HepG2-Nu2), derived from 2.2.15 cells, were used as an in vitro model to determine the efficacy of thymosin-α 1 and interferon-α, individually and combined, a proliferation inhibitors of HBV-infected cells. For comparison, parental HepG2 cells and an SV40-transfected HepG2 cell line (HepG2P9T2) were also evaluated. Results: In a clonogenic soft agar assay, thymosin-α 1 inhibited the anchorage-independent growth of the HepG2-Nu2 cells by 40% compared with untreated controls, but did not inhibit parental HepG2 or HepG2P9T2 clonal growth. The response was dose dependent over concentrations spanning three log units. In comparison, 10 000 units/ml of interferon-α inhibited parental HepG2, HepG2-N4Z and HepG2P9T2 by 33%, 41% and 87%, respectively. The combination of thymosin-α 1 and interferon-α consistently inhibited HepG2-Nu2 clonal growth more effectively than either treatment alone, reaching maximum inhibition levels of 51%. Conclusions: Thymosin-α 1 specifically inhibits the tumorigenic growth of HBV-transfected HepG2 cells in contrast to the general inhibition displayed by interferon-α. This panel of cell lines may be an important resource for dissecting the mechanism by which thymosin, alone or in combination with other drugs, influences HBV-infected hepatocytes and/or HBV-associated carcinoma.