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).
Conclusion: Combined use of AFP antisense oligomers and 5-FU could more effectively inhibit the growth of BEL-7404 human hepatoma cells in vitro.