Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides.
In previous work, we saw that interleukin-6 (IL-6), a multifunctional cytokine, is produced by epithelial ovarian cancer cells and that ovarian cancer cells express the IL-6 receptor. Here, we examined the possibility that IL-6 acts as an autocrine growth factor for ovarian cancer cells. Inhibition of IL-6 gene expression by exposure to IL-6 antisense oligonucleotides resulted in greatly decreased cellular proliferation. Exposure of ovarian cancer cell lines (CAOV-3, OVCAR-3, and OC-436), to 1-5 microM of a 15-base single-stranded antisense IL-6 oligodeoxynucleotide, specific for a sequence in the second coding exon of the IL-6 gene, resulted in decreased IL-6 production and a > 80-85% inhibition of cellular proliferation. However, the addition of exogenous IL-6 failed to restore the proliferation of the antisense-treated cells. Antibodies to IL-6 did not consistently inhibit cell growth nor did rIL-6 enhance precursor frequency in a limiting dilution analysis. These results suggest that IL-6 does not directly induce the proliferation of ovarian cancer cells although endogenous IL-6 production is needed for optimal cell growth. As the majority of epithelial ovarian cancers produce IL-6, the direct specific inhibition of IL-6 gene expression is of potential therapeutic value.
Watson
J M
JM
Department of Microbiology & Immunology, UCLA School of Medicine.
Berek
J S
JS
Martínez-Maza
O
O
D001483:Base Sequence; D015152:Blotting, Northern; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins