Antihepatoma effect of alpha-fetoprotein antisense phosphorothioate oligodeoxyribonucleotides in vitro and in mice.
OBJECTIVE
To evaluate antihepatoma effect of antisense phosphorothioate oligodeoxyribonucleotides (S-ODNs) targeted to alpha-fetoprotein (AFP) genes in vitro and in nude mice.


METHODS
AFP gene expression was examined by immunocytochemical method or enzyme-linked immunosorbent assay. Effect of S-ODNs on SMMC-7721 human hepatoma cell growth in vitro was determined using microculture tetrazolium assay. In vitro 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. Specific antisense S-ODNs, but not control S-ODNs, inhibited the growth of hepatoma cells in vitro. In vitro, only antisense S-ODNs exhibited obvious antitumor activities. FACS analysis revealed that the growth inhibition by antisense S-ODNs was associated with their cell apoptosis induction.


CONCLUSIONS
Antisense S-ODNs targeted to AFP genes inhibit the growth of human hepatoma cells and solid hepatoma, which is related to their cell apoptosis induction.
Wang
X W
XW
Department of Biotherapy, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Yuan
J H
JH
Zhang
R G
RG
Guo
L X
LX
Xie
Y
Y
Xie
H
H
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000235:genetics*
D020319:Oligodeoxyribonucleotides, Antisense; D000509:alpha-Fetoproteins