Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice

AIM To evaluate antihepatoma effect of antisense phosphorothioate oligodeox yribonucleotides (S-ODNs) targeted to alphafetoprotein (AFP) genes in vitro and in nude mice. METHODS AFP gene expression was examined by immunocytochemical method or en zyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepato ma cell growth in vitro was determined using microculture tetrazolium assay . In vivo antitumor activities of S-ODNs were monitored by measuring tumor weight differences in treated and control mice bearing SMMC-7721 xenografts . Induction of cell apoptosis was evaluated by fluorescence-activated cell sorter (FACS) analysis. RESULTS Antisense S-ODN treatment led to reduced AFP gene expression. Speci fic antisense S-ODNs, but not control S-ODNs, inhibited the growth of heapt oma cells in vitro. In vivo, only antisense S-ODNs exhibited obvious antitu mor activities. FACS analysis revealed that the growth inhibition by antise nse S-ODNs was associated with their cell apoptosis induction. CONCLUSION Antisense S-ODNs targeted to AFP genes inhibit the growth of hum an hepatoma cells and solid hepatoma, which is related to their cell apopto sis induction.