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.