Maeda M, Watanabe N, Tsuji N, Tsuji Y, Okamoto T, Sasaki H, Akiyama S, Niitsu Y
Department of Internal Medicine (Section 4), Sapporo Medical College.
Jpn J Cancer Res. 1993 Aug;84(8):921-7. doi: 10.1111/j.1349-7006.1993.tb02067.x.
The synergistic antitumor effect of tumor necrosis factor (TNF) and granulocyte colony-stimulating factor (G-CSF) was investigated. G-CSF was administered subcutaneously to BALB/c mice inoculated with Meth-A cells at a dose of 2.5 micrograms/day for 5 consecutive days. When TNF (1 x 10(3) U) was administered intravenously to mice which had been pretreated with G-CSF, tumor growth showed a 74.1% inhibition 17 days after the tumor cell inoculation, compared to that of untreated mice. In this experiment, G-CSF significantly (P < 0.025) enhanced the antitumor effect of TNF. The in vitro cytotoxicity of TNF (10 U/ml) towards Meth-A cells was increased about 5.2-fold in the presence of neutrophils (E/T = 50) as compared to the cytotoxicity obtained with TNF alone. A combination of TNF and G-CSF (50 ng/ml) in the presence of neutrophils, resulted in a 2.1 times greater cytotoxicity against Meth-A cells as compared to that obtained without G-CSF. Significant augmenting effects of G-CSF on superoxide (O2-) production by TNF-stimulated neutrophils were observed. These observation suggest that the neutrophil plays an important role in the antitumor action of TNF on Meth-A cells, and that the antitumor effect of TNF is enhanced by combination with G-CSF.
研究了肿瘤坏死因子（TNF）和粒细胞集落刺激因子（G-CSF）的协同抗肿瘤作用。以2.5微克/天的剂量对接种了Meth-A细胞的BALB/c小鼠皮下注射G-CSF，连续5天。当对预先用G-CSF处理过的小鼠静脉注射TNF（1×10³单位）时，与未处理的小鼠相比，在接种肿瘤细胞17天后肿瘤生长受到74.1%的抑制。在本实验中，G-CSF显著（P<0.025）增强了TNF的抗肿瘤作用。与单独使用TNF时相比，在存在中性粒细胞（E/T = 50）的情况下，TNF（10单位/毫升）对Meth-A细胞的体外细胞毒性增加了约5.2倍。在存在中性粒细胞的情况下，TNF与G-CSF（50纳克/毫升）联合使用，对Meth-A细胞的细胞毒性比不使用G-CSF时高2.1倍。观察到G-CSF对TNF刺激的中性粒细胞产生超氧化物（O₂⁻）有显著增强作用。这些观察结果表明，中性粒细胞在TNF对Meth-A细胞的抗肿瘤作用中起重要作用，并且TNF与G-CSF联合使用可增强其抗肿瘤效果。
