Keller E T, Ershler W B
Institute on Aging, University of Wisconsin-Madison, Madison 53706, USA.
J Immunol. 1995 Apr 15;154(8):4091-8.
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.
白细胞介素-6（IL-6）可刺激包括淋巴瘤和骨髓瘤在内的多种肿瘤的增殖；因此，抑制IL-6可能会减缓这些肿瘤的生长。相应地，我们研究了IL-6和IL-6受体反义硫代磷酸化寡脱氧核苷酸（ODN）对IL-6反应性（U266）和无反应性（RPMI 8226）骨髓瘤细胞系增殖的影响。细胞在有或无IL-6的情况下培养，并添加针对IL-6或IL-6受体的反义序列。通过竞争性聚合酶链反应（C-PCR）评估细胞的增殖情况（[3H]胸腺嘧啶核苷摄取）以及IL-6和IL-6受体mRNA的稳态水平。在无IL-6的情况下，IL-6反义ODN可显著降低U266细胞的增殖，但在有IL-6存在时则不然。相反，IL-6受体反义ODN在有和无IL-6的情况下均能抑制U266细胞的增殖。正如预期的那样，IL-6和IL-6受体反义ODN对RPMI 8226细胞的增殖均无影响。C-PCR显示，分别暴露于IL-6 ODN和IL-6受体ODN的细胞中，IL-6和IL-6受体mRNA显著且特异性地减少。这些结果表明，在治疗环境中，IL-6受体反义ODN可能比IL-6反义序列更有效地抑制IL-6刺激的细胞。
