[Effects of ciclosporin and tacrolimus on replication of hepatitis B virus in vitro: a comparative study].
OBJECTIVE
To investigate the effects of ciclosporin (CsA) and tacrolimus (FK506) on replication of hepatitis B virus (HBV) in vitro.


METHODS
HBV genome permanently transfected human liver cancer cells of the line HepG2.2.15 were cultured. CsA and FK506 at different concentrations were added into the culture fluid so as to identify the nontoxic concentrations by MTT method. Then the HepG2.2.15 cells were treated by CsA and FK506 at different nontoxic concentrations respectively for 4 days. ELISA was used to detect the HB surface antigen (HBsAg) and HB e antigen (HBeAg) in the supernatant. The relative replication level of HBV DNA was detected by slot blot analysis.


RESULTS
MTT method confirmed that the nontoxic concentrations of CsA and FK506 were 0-40.0 microg/ml and 0-400 ng/ml respectively. After the treatment of CsA at the concentration of 1.3, 2.5, and 5.0 microg/ml, in comparison to the control group, the suppression rates of HBsAg expression in the HepG2.2.15 cells were 16.5% +/- 9.4%, 21.5% +/- 8.9%, and 33.1% +/- 5.3% respectively (all P < 0.05); the suppression rates of HBeAg expression in the HepG2.2.15 cells were 7.8% +/- 2.2%, 11.0% +/- 2.3%, and 20.8% +/- 1.5% respectively (all P < 0.05); and the HBV DNA replication levels were 56 +/- 16, 42 +/- 11, and 40 +/- 10 respectively (P > 0.05, P < 0.05, and P > 0.05). However, FK506 at different nontoxic concentrations showed no significant inhibitory effect on the levels of HBsAg, HBeAg, and HBV DNA.


CONCLUSIONS
CsA dose-dependently inhibits the HBV replication in vitro, and FK506 does not exercise similar effects.
Xia
Wei-liang
WL
Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Xie
Hai-yang
HY
Shen
Yan
Y
Wu
Li-ming
LM
Zhang
Feng
F
Zheng
Shu-sen
SS
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D016559:Tacrolimus / Q000494:pharmacology*; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016572:Cyclosporine; D016559:Tacrolimus