title: Inhibition of growth of human hepatoma cells by dual-function antisense IL-6 oligonucleotides.
abstract: Hepatocellular lineage cell lines (two hepatoma and Chang liver cell lines) were found to produce interleukin-6 (IL-6). As the human hepatoma cell line, HCC-M expresses mRNA for both IL-6 and IL-6 receptor, we examined the possibility that IL-6 acted as an autocrine growth factor for HCC-M cells using two IL-6 antisense oligonucleotides (AS-1 and AS-2 oligomers) which were synthesized from different regions of an IL-6 cDNA clone. Both IL-6 antisense oligonucleotides inhibited the growth of HCC-M cells within 48 h (% inhibition by AS-1 and AS-2 oligomers was 53 and 21%, respectively). Although inhibition of HCC-M cell growth induced by AS-2 oligomer was restored by addition of exogenous recombinant IL-6 (rIL-6), the inhibition of growth induced by AS-1 oligomer was not fully restored by exogenous rIL-6, implicating the involvement of a nonantisense mechanism associated with four contiguous guanosine residues in this sequence. The inhibitory effect of AS-2 oligomer was attenuated after 72 h (% inhibition was 8%), whereas the AS-1 oligomer-induced inhibition of growth was sustained beyond 72 h (% inhibition was 38--39%). Therefore, these dual-function oligonucleotides that act via both an antisense and nonantisense mechanism may be of potential therapeutic value against hepatoma.
authors.affiliation: Department of Internal Medicine, Research Center for Liver Disease, Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, 108-8642, Tokyo, Japan
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumagai
authors.forename: Kanji
authors.initials: K
authors.lastname: Tsuchimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsunematsu
authors.forename: Kyoko
authors.initials: K
authors.lastname: Toda
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Saito
authors.forename: Toshio
authors.initials: T
authors.lastname: Morizane
authors.forename: Masaharu
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii