Lavnikova N, Burdelya L, Lakhotia A, Patel N, Prokhorova S, Laskin D L
Rutgers University, Piscataway, New Jersey 08855-0789, USA.
J Leukoc Biol. 1997 Apr;61(4):452-8. doi: 10.1002/jlb.61.4.452.
Nitric oxide has been shown to contribute to cytotoxicity in mouse and rat tumor cells. In these studies we examined the role of nitric oxide in cytostasis in hamster tumor cells varying in their malignant potential. Spontaneously transformed hamster embryonic fibroblasts (STHE cells) with low metastatic activity produced significantly greater amounts of nitric oxide in response to interleukin-1 (IL-1) or lipopolysaccharide (LPS)-activated hamster alveolar macrophages (HAM) than did tumor cell lines with high experimental metastatic activity (HET-SR, HET-SR1, STHE-83/20 cells). HET-SR cells, which exhibit low spontaneous metastastic activity, also produced relatively high levels of nitric oxide in response to IL-1, whereas the response of the spontaneously metastatic lines, HET-SR1 and STHE-83/20 cells, was low. IL-1 and HAM also induced cytostasis in nitric oxide-producing STHE and HET-SR cells. However, the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), had no effect on this activity. These findings, together with the observation that anti-tumor necrosis factor alpha antibody prevented HAM-mediated cytostasis in all of the tumor cell lines demonstrate that nitric oxide is not involved in hamster macrophage-induced tumor cell growth suppression. In contrast to HAM, rat alveolar macrophages, which produced nitric oxide in response to LPS, exerted similar levels of cytostasis toward all of the hamster tumor cell variants, an action that was blocked by L-NMMA in HET-SR, HET-SR1, and STHE-83/20 cells. Thus production of nitric oxide by hamster tumor cells is inversely correlated with their malignant potential. However, nitric oxide does not appear to be involved in IL-1- or HAM-mediated cytostasis toward hamster tumor cells.
一氧化氮已被证明可导致小鼠和大鼠肿瘤细胞的细胞毒性。在这些研究中，我们检测了一氧化氮在具有不同恶性潜能的仓鼠肿瘤细胞的细胞生长抑制中的作用。与具有高实验性转移活性的肿瘤细胞系（HET-SR、HET-SR1、STHE-83/20细胞）相比，具有低转移活性的自发转化仓鼠胚胎成纤维细胞（STHE细胞）在受到白细胞介素-1（IL-1）或脂多糖（LPS）激活的仓鼠肺泡巨噬细胞（HAM）刺激时，产生的一氧化氮量显著更多。具有低自发转移活性的HET-SR细胞在受到IL-1刺激时也产生相对高水平的一氧化氮，而自发转移细胞系HET-SR1和STHE-83/20细胞的反应则较低。IL-1和HAM也可诱导产生一氧化氮的STHE和HET-SR细胞发生细胞生长抑制。然而，一氧化氮合酶抑制剂N(G)-单甲基-L-精氨酸（L-NMMA）对该活性没有影响。这些发现，连同抗肿瘤坏死因子α抗体可阻止所有肿瘤细胞系中HAM介导的细胞生长抑制这一观察结果，表明一氧化氮不参与仓鼠巨噬细胞诱导的肿瘤细胞生长抑制。与HAM不同，大鼠肺泡巨噬细胞在受到LPS刺激时产生一氧化氮，对所有仓鼠肿瘤细胞变体都表现出相似程度的细胞生长抑制作用，在HET-SR、HET-SR1和STHE-83/20细胞中，L-NMMA可阻断这一作用。因此，仓鼠肿瘤细胞产生一氧化氮的量与其恶性潜能呈负相关。然而，一氧化氮似乎不参与IL-1或HAM介导的对仓鼠肿瘤细胞的细胞生长抑制作用。
