Cytostatic and cytotoxic activity of tumor necrosis factor on human cancer cells.
Cytostatic and cytotoxic activity of tumor necrosis factor on human cancer cells.
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DOI：
10.4049/jimmunol.138.8.2711
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发表时间：
1987-04
影响因子：
4.4
通讯作者：
V. Ruggiero;K. Latham;C. Baglioni
中科院分区：
文献类型：
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作者：
V. Ruggiero;K. Latham;C. Baglioni
研究了人重组肿瘤坏死因子（rTNF）在不同肿瘤细胞系上的抑细胞活性和细胞毒活性。rTNF可抑制人BT-20乳腺癌和ME-180宫颈癌细胞的生长，而其他两种细胞系则没有明显的抑制作用。然而，当蛋白质合成被环己亚胺抑制时，rTNF对这些细胞有细胞毒性，而对BT-20细胞没有细胞毒性。这一发现表明，不同的机制负责rTNF的细胞抑制和细胞毒性活性。不同细胞系对rTNF的敏感性与rTNF受体的高数量或亲和力无关。仅占据少数受体就足以产生rTNA的细胞毒性，但干扰素- γ处理后受体数量增加或环己亚胺预处理后受体数量减少，相应地增强或抑制rTNF的细胞毒性。似乎有些细胞可以通过合成“保护性”蛋白来保护自己免受rTNF的影响。在寻找这些蛋白的过程中，我们观察到rTNF诱导SK-MEL-109黑色素瘤细胞中两种多肽的合成，而在其他癌细胞中则没有。加入rTNF的放线菌素D可抑制这些多肽的合成，表明rTNF可诱导相应mrna的转录。令人惊讶的是，rTNF刺激了在低血清培养基中培养的SK-MEL-109细胞的生长。
The cytostatic and cytotoxic activity of human recombinant tumor necrosis factor (rTNF) was assayed on different tumor cell lines. Human BT-20 breast and ME-180 cervix cancer cells were growth-inhibited by rTNF, whereas two other cell lines were not significantly inhibited. However, when protein synthesis was inhibited by cycloheximide, rTNF was cytotoxic for these cells but not for BT-20 cells. This finding suggested that different mechanisms are responsible for the cytostatic and cytotoxic activity of rTNF. The sensitivity of different cell lines to rTNF could not be correlated with a high number or affinity of rTNF receptors. Occupancy of only a few receptors was sufficient for rTNA cytotoxicity, but an increase in receptor number after treatment with interferon-gamma, or a decrease after pretreatment with cycloheximide, correspondingly enhanced or depressed the cytotoxicity of rTNF. It seemed possible that some cells could be protected from this effect of rTNF by synthesizing "protective" proteins. While searching for such proteins, we observed that rTNF induced the synthesis of two polypeptides in SK-MEL-109 melanoma cells, but not in other cancer cells. Actinomycin D added with rTNF abolished synthesis of these polypeptides, suggesting that rTNF induced transcription of the corresponding mRNAs. Surprisingly, rTNF stimulated growth of SK-MEL-109 cells cultured in medium with low serum.