EFFECT OF IL-6 RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDE ON IN-VITRO PROLIFERATION OF MYELOMA CELLS

IL-6 stimulates proliferation of various tumors, including lymphoma an d myeloma; thus, inhibiting IL-6 may decrease the growth of these tumo rs. Accordingly, we examined the effect of IL-6 and IL-6R antisense ph ospho-rothioated oligodeoxynucleotides (ODNs) on proliferation of IL-6 responsive (U266) and nonresponsive (RPMI 8226) myeloma cell lines. C ells were grown in the presence or absence of IL-6, with added antisen se to either IL-6 or IL-6R. Cells were evaluated for proliferation ([H -3]thymidine uptake) and steady state levels of both IL-6 and IL-6R mR NA by competitive PCR (C-PCR). Proliferation of U266 cells was decreas ed markedly by IL-6 antisense ODN in the absence of IL-6, but not in i ts 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 prol iferation. C-PCR demonstrated a marked and specific decrease of IL-6 a nd 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 effecti ve inhibitor of IL-6-stimulated cells than IL-6 antisense in a therape utic setting.