Inhibition of .ALPHA.-Fetoprotein Production in a Hepatoma Cell Line by Antisense Oligonucleotide Analogues.

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  • Lin Shwu-Bin
    Graduate Institute of Medical Technology, Department of Clinical Pathology, National Taiwan University
  • Huang Shyh-Shin
    Graduate Institute of Medical Technology, Department of Clinical Pathology, National Taiwan University
  • Choo Kong-Bung
    Department of Medical Research, Veterans General Hospital-Taipei
  • Chen Pei-Jer
    Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
  • Au Lo-Chun
    Department of Medical Research, Veterans General Hospital-Taipei

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α-Fetoprotein (AFP) is a fetal protein which is absent in adult serum. However, the AFP gene is expressed in some neoplastic cells. According to the literature, AFP may play a role in accelerating the growth of cancer cells. In this report, 15meric antisense oligonucleotide analogues (phosphorothioates and methylphosphonates) and their chimeric forms, which were complementary to different regions of AFP mRNA, were synthesized, and their physical characteristics such as stability, melting temperature, and toxicity were compared. They were examined as to their inhibitory effects on the translation of AFP mRNA in a AFP-producing hepatoma cell line, HuH-7. We found that chimeric oligomers with methylphosphonate or phosphorothioate linkages at both the 5' and 3' ends were more effective than prototypic oligomers. Inhibition of 72% was achieved with a chimeric oligomer against the translational initiation region, at a concentration of 25 μM. No suppressive effect of the oligomers was observed on cell viability or albumin production, indicating the specificity of the inhibition.

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