Effect of IL-6 receptor antisense oligodeoxynucleotide on in vitro proliferation of myeloma cells

Abstract

IL-6 stimulates proliferation of various tumors, including lymphoma and myeloma; thus, inhibiting IL-6 may decrease the growth of these tumors. Accordingly, we examined the effect of IL-6 and IL-6R antisense phosphorothioated oligodeoxynucleotides (ODNs) on proliferation of IL-6 responsive (U266) and nonresponsive (RPMI 8226) myeloma cell lines. Cells were grown in the presence or absence of IL-6, with added antisense to either IL-6 or IL-6R. Cells were evaluated for proliferation ([3H]thymidine uptake) and steady state levels of both IL-6 and IL-6R mRNA by competitive PCR (C-PCR). Proliferation of U266 cells was decreased markedly by IL-6 antisense ODN in the absence of IL-6, but not in its presence. In contrast, IL-6R antisense ODN inhibited proliferation of U266 cells in both the presence and absence of IL-6. As anticipated, neither IL-6 nor IL-6R antisense ODN had an effect on RPMI 8226 proliferation. C-PCR demonstrated a marked and specific decrease of IL-6 and IL-6R mRNA in cells exposed to IL-6 ODN and IL-6R ODN, respectively. These results suggest that IL-6R antisense ODN may be a more effective inhibitor of IL-6-stimulated cells than IL-6 antisense in a therapeutic setting.