Abstract: Objective To investigate the effect of dexamethasone (DEX), cyclophosphamide (CYP) and tacrolimus (FK506) on DNA replication and protein synthesis of hepatitis B virus (HBV) in vitro. Methods HepG2.2.15 cell line was treated with different concentrations of DEX, CYP or FK506, and safe concentrations of the three immunosupressive drugs were identified using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the cell culture supernatant were detected with electrochemiluminescence immunoassay. The intracellular HBV DNA level was evaluated with Southern blot. HBV expression and replication were assessed according to HBsAg, HBeAg and HBV DNA level. Results The safe concentration range of DEX, CYP and FK506 was 0～500 μg/mL, 0～1000 μg/mL and 0～10 μg/mL, respectively. Compared with control group, FK506 group showed no significant difference in the levels of HBsAg, HBeAg and HBV DNA. CYP group showed higher levels of HBsAg (P<0.05), while no significant difference in the levels of HBeAg and HBV DNA (P>0.05). DEX group showed lower levels of HBsAg and HBeAg (P<0.05), while no significant difference in HBV DNA (P>0.05). Conclusion In the safe concentration range, FK506 has no direct inhibitory or promoting effect on HBV DNA replication. CYP treatment could increase HBsAg expression, but have no effect on HBeAg expression and HBV DNA replication. DEX treatment could inhibit the expression of HBsAg or HBeAg, but has no inhibitory effect on HBV DNA replication.

Key words: Immunosupressive drugs, Hepatitis B virus, HepG2.2.15 cell