Ishihara J, Saijo N, Sasaki Y, Nakano H, Ozaki A, Takahashi H, Sakurai M, Nakagawa K, Iigo M, Kanzawa F
Cancer Immunol Immunother. 1987;24(3):185-9. doi: 10.1007/BF00205627.
The antitumor effect of recombinant human tumor necrosis factor (rH-TNF) on two clones of rat fibrosarcoma with different metastatic potential to lymph nodes was examined. The colony formation of clone A, which has high metastatic potential, was completely inhibited by continuous exposure to rH-TNF at 50 U/ml. In contrast, colony formation of clone G, which has low metastatic potential, was not inhibited by high concentrations of rH-TNF (10,000 U/ml). The inhibitory effect of rH-TNF on colony formation by clone A was also observed with a 1-h exposure to rH-TNF. This effect was time and concentration dependent, as determined by the colony assay, 3H-thymidine uptake assay, and 51Cr-release assay. 3H-thymidine and 3H-uridine uptake per cell of clone A exposed to rH-TNF was not decreased. This suggests that the mechanisms of the antitumor effect of rH-TNF were not due to inhibition of DNA and RNA synthesis of tumor cells. In vivo growth and lymph node metastases of clone A inoculated i.p. to Donryu strain rats were completely suppressed by 14 consecutive i.p. injections of 10(5) or 10(6) U/kg per day of rH-TNF. On the other hand the growth of clone G was not influenced by rH-TNF administration.
研究了重组人肿瘤坏死因子（rH-TNF）对两种具有不同淋巴结转移潜能的大鼠纤维肉瘤克隆的抗肿瘤作用。具有高转移潜能的克隆A的集落形成在持续暴露于50 U/ml的rH-TNF时被完全抑制。相比之下，具有低转移潜能的克隆G的集落形成在高浓度的rH-TNF（10,000 U/ml）下未被抑制。克隆A的集落形成在暴露于rH-TNF 1小时后也观察到了rH-TNF的抑制作用。通过集落测定、3H-胸腺嘧啶核苷摄取测定和51Cr释放测定确定，这种作用具有时间和浓度依赖性。暴露于rH-TNF的克隆A的每个细胞的3H-胸腺嘧啶核苷和3H-尿苷摄取未降低。这表明rH-TNF的抗肿瘤作用机制不是由于抑制肿瘤细胞的DNA和RNA合成。通过每天腹腔注射10(5)或10(6) U/kg的rH-TNF连续14次腹腔注射，完全抑制了接种到Donryu品系大鼠腹腔内的克隆A的体内生长和淋巴结转移。另一方面，克隆G的生长不受rH-TNF给药的影响。
