Balkwill F R, Goldstein L, Stebbing N
Int J Cancer. 1985 May 15;35(5):613-7. doi: 10.1002/ijc.2910350508.
Six different pure human interferons (IFNs), were tested for anti-tumour effect against two human carcinomas, breast and bowel, growing in nude mice, in a total of 36 experiments. The IFN-alpha mixture, analogue and subtypes showed the greatest activity, particularly against the breast cancer xenograft, whereas IFN-beta and IFN-gamma had little effect. However, circulating IFN could be found in the sera of mice treated with all 3 IFN types. In terms of amount of IFN protein, IFN-alpha Con1, an IFN-alpha analogue, was the most effective, a dose of 0.1 micrograms/mouse/day being sufficient to induce breast tumour regression, and IFN-gamma the least effective, a dose of 10 micrograms/mouse/day having no effect on the same tumour. A more detailed comparison of 2 IFN-alpha subtypes showed that a daily dose of 1 microgram IFN-alpha A was more effective than the same dose of IFN-alpha D, but as this IFN had approximately 30 times less antiviral activity on human cells than IFN-alpha D, these IFNs were probably at least equally effective in terms of human cell units. IFN-alpha D stimulated mouse spleen natural killer cell activity but it was not clear whether this stimulation was involved in anti-tumour activity. We conclude that this model system is useful for investigating direct anti-tumour activity of a wide range of IFN types and subtypes.
在总共36项实验中，对六种不同的纯人干扰素（IFN）进行了测试，以研究其对在裸鼠体内生长的两种人类癌症——乳腺癌和肠癌的抗肿瘤作用。α干扰素混合物、类似物和亚型表现出最大的活性，尤其是对乳腺癌异种移植瘤，而β干扰素和γ干扰素几乎没有效果。然而，在用所有三种干扰素类型处理的小鼠血清中都能检测到循环干扰素。就干扰素蛋白的量而言，α干扰素类似物Con1最有效，每天每只小鼠0.1微克的剂量足以诱导乳腺肿瘤消退，而γ干扰素最无效，每天每只小鼠10微克的剂量对同一肿瘤没有影响。对两种α干扰素亚型进行更详细的比较表明，每天1微克的α干扰素A比相同剂量的α干扰素D更有效，但由于这种干扰素对人类细胞的抗病毒活性比α干扰素D低约30倍，就人类细胞单位而言，这些干扰素可能至少同样有效。α干扰素D刺激小鼠脾脏自然杀伤细胞活性，但不清楚这种刺激是否与抗肿瘤活性有关。我们得出结论，该模型系统对于研究多种干扰素类型和亚型的直接抗肿瘤活性很有用。
