Combined effect of alpha-fetoprotein antisense oligodeoxy-nucleotides and 5-fluorouracil on human hepatoma cell growth.
OBJECTIVE
To investigate the effect of alpha-fetoprotein (AFP) antisense phosphorothioate oligodeoxynucleotides in combination with 5-fluorouracil (5-FU) on the growth of BEL-7404 human hepatoma cells in vitro.


METHODS
Phosphorothioate oligodeoxynucleotides were synthesized by beta-cyanoethyl-phosphoramidite chemistry. AFP gene expression in human hepatoma cells was determined by avidin-biotin-peroxidase complex (ABC) immunocytochemical method. Cell growth in the presence or absence of experimental agents was measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny ltetrazolium (MTT) microculture tetrazolium assay.


RESULTS
AFP antisense oligomers markedly suppressed the growth of BEL-7404 human hepatoma cells in vitro by sequence-specific blocking of the AFP gene expression in the cells (P < 0.05). 5-FU also inhibited the hepatoma cell growth in a dose-dependent manner when used alone (P < 0.05). The combined treatment with AFP antisense oligomers and 5-FU showed significantly enhanced hepatoma cell growth inhibition than either AFP antisense or 5-FU treated cells alone (P < 0.05).


CONCLUSIONS
Combined use of AFP antisense oligomers and 5-FU could more effectively inhibit the growth of BEL-7404 human hepatoma cells in vitro.
Wang
X
X
Department of Biotherapy, Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Zhang
R
R
Xie
H
H
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D020319:Oligodeoxyribonucleotides, Antisense; D000509:alpha-Fetoproteins; D005472:Fluorouracil