Munker M, Munker R, Saxton R E, Koeffler H P
Cancer Res. 1987 Aug 1;47(15):4081-5.
The modulation of clonal growth of cells of 15 human lung cancer lines was examined by coculture with different recombinant lymphokines, monokines, and several agents which induce differentiation in other malignant cell systems. Recombinant human tumor necrosis factor alpha (TNF) was inhibitory to all non-small cell lung cancer cell lines with a 50% effective dose of clonal inhibition (ED50) in the range of 30-2000 units/ml. Two representative squamous lines (SK-MES and P3) had 150 to 250 high affinity (Kd approximately equal to pM) cell surface TNF receptors. In contrast, clonal growth of small cell lung cancer lines was not inhibited by TNF, and two representative lines (H69c and R592) expressed negligible cell surface TNF receptors. Recombinant alpha, beta, and gamma interferons (4000 units/ml) each inhibited greater than or equal to 30% clonal growth of more than 50% of the non-small cell lung cancer lines. TNF (100-1000 units/ml) in combination with gamma-interferon was synergistic in the inhibition of clonal growth of these cells. Further studies showed that synergism of clonal inhibition occurred even when the cells were initially exposed to gamma-interferon, washed, and plated in soft agar with TNF. All-trans-retinoic acid (ED50, 5 X 10(-7)-10(-6) M), dimethyl sulfoxide (ED50, 1.2-1.6%), and 12-O-tetradecanoylphorbol-13-acetate (ED50, 5 X 10(-8)-10(-10) M) inhibited clonal proliferation of 7 of 9, 7 of 9, and 8 of 9 non-small cell lung cancer lines, respectively. In contrast, clonal proliferation of cells of small cell lung cancer lines was decreased only slightly at almost all concentrations of each of the agents. Interleukin-1 and -2 and granulocyte-monocyte colony-stimulating factor had no effect on the clonal growth of any of the lung cancer lines. Our results suggest that TNF in combination with gamma-interferon may be therapeutically active for some patients with non-small cell lung cancer, but small cell lung cancer probably will be unresponsive to all the agents that we examined.
通过与不同的重组淋巴因子、单核因子以及几种在其他恶性细胞系统中诱导分化的试剂共培养，研究了15种人肺癌细胞系的克隆生长调节情况。重组人肿瘤坏死因子α（TNF）对所有非小细胞肺癌细胞系均有抑制作用，克隆抑制的50%有效剂量（ED50）在30 - 2000单位/毫升范围内。两个代表性的鳞癌细胞系（SK - MES和P3）具有150至250个高亲和力（Kd约等于皮摩尔）的细胞表面TNF受体。相比之下，小细胞肺癌细胞系的克隆生长不受TNF抑制，两个代表性细胞系（H69c和R592）表达的细胞表面TNF受体可忽略不计。重组α、β和γ干扰素（4000单位/毫升）分别抑制了超过50%的非小细胞肺癌细胞系中大于或等于30%的克隆生长。TNF（100 - 1000单位/毫升）与γ干扰素联合使用对这些细胞克隆生长的抑制具有协同作用。进一步研究表明，即使细胞最初暴露于γ干扰素，洗涤后再与TNF一起接种于软琼脂中，克隆抑制的协同作用依然会发生。全反式维甲酸（ED50，5×10⁻⁷ - 10⁻⁶ M）、二甲基亚砜（ED50，1.2 - 1.6%）和12 - O - 十四酰佛波醇 - 13 - 乙酸酯（ED50，5×10⁻⁸ - 10⁻¹⁰ M）分别抑制了9个非小细胞肺癌细胞系中的7个、9个中的7个和9个中的8个的克隆增殖。相比之下，在几乎所有浓度的每种试剂作用下，小细胞肺癌细胞系的克隆增殖仅略有下降。白细胞介素 - 1和 - 2以及粒细胞 - 单核细胞集落刺激因子对任何肺癌细胞系的克隆生长均无影响。我们的结果表明，TNF与γ干扰素联合使用可能对一些非小细胞肺癌患者具有治疗活性，但小细胞肺癌可能对我们所检测的所有试剂均无反应。
