This paper was to investigate the inhibitory effects against HBV of a phosphorothioate antisense oligodeoxynucleotide "ASODN"
targeted to ASGPR combined with anti-HBV drugs in vitro.The assay attempted to access a new method and idea to refresh the thinking way about hepatitis B treatment by the combination of ASODN and drugs.A phosphorothioate antisense oligodeoxynucleotide targeted to asialoglycoprotein receptor(ASGPR) mRNA was synthesized.Using HepG2.2.15 cell as the target cell,ASODN was transfected into HepG2.2.15 cell by lipofectin.Six hours after the incubation of ASODNs,the medium was replaced with different concentrations of Lamivudine(3TC) and Adefovir Dipivoxil(ADV) and cultures were incubated for 72h.Then cell media were collected and detected.HBV DNA level in cell medium was examined by real-time PCR.HBsAg and HBeAg were detected by ELISA.Jin Zhengjun Method was applied to evaluate the interaction of ASODN and the anti-HBV drugs.Results showed that 3TC or ADV accompanying with ASODN separately showed an additive or
synergistic effect towards the inhibition of HBsAg. With the increasing of ADV concentration,the
Synergistic effect between the two drugs declined gradually.The combination of 3TC and ASDON showed antagonistic,additive or synergistic effects on HBeAg.Especially,antagonistic effect decreased gradually along with the increasing of 3TC concentration.Meanwhile, the combined use of ADV and ASODN demonstrated the additive effect only on the inhibitive effect of HBeAg.The combined process of 3TC and ADV respectively with ASDON displayed the additive or synergistic effect on suppressing of HBV DNA.When ADV 0.5μmol/L combined with ASODN 0.2μmol/L,the inhibitive rate against HBV DNA could be promoted to 72.6%.It is concluded that under certain experimental conditions,the combination of ASODN with 3TC and ADV respectively displayed the additive or synergistic effect against HBV.Especially the inhibition of HBsAg was significant.