Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1.
Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1.
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发表时间：
1991-10
期刊：
影响因子：
11.2
通讯作者：
C. Pontzer;F. Bazer;Howard M. Johnson
中科院分区：
文献类型：
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作者：
C. Pontzer;F. Bazer;Howard M. Johnson
绵羊滋养层蛋白-1（oTP-1）是α-干扰素（IFN α）变体，由孕体分泌，称为I型滋养层干扰素，负责绵羊妊娠的母体识别。我们以前已经表明，oTP-1是作为任何已知的干扰素有效的抗病毒剂。IFN还具有抗细胞活性，并且实际上用于癌症治疗，并且已经发现其在治疗癌症如骨髓性和毛细胞白血病中是有效的。目前使用的IFN的一个显著问题是在高浓度下的不希望的毒性副作用。在这项研究中，我们研究了oTP-1的抗细胞活性和毒性。它抑制增殖，但在高浓度下不显示毒性，不像已知的IFN α S。在使用人上皮细胞系WISH和牛上皮细胞系MDBK的集落形成的抗细胞试验中，oTP-1抑制集落大小和数量。oTP-1分别对人和牛细胞与人和牛IFN α一样有效;因此，它显示出有效的跨物种活性。其活性呈剂量依赖性，在低至1单位/ml的浓度下即可观察到增殖抑制。浓度高达50，000单位/毫升停止增殖，而活力不受损害。细胞周期分析显示，oTP-1处理48 h后，S期细胞比例增加，G2/M期细胞比例相应减少。因此，oTP-1似乎抑制细胞通过S期的进展。oTP-1的抗增殖作用早在培养开始后12小时就可以观察到，并维持6天。因此，oTP-1表现出有效的抗细胞活性，而没有跨物种的毒性，并且可能具有作为抗肿瘤剂的治疗潜力，而没有通常与IFN相关的毒性作用。
Ovine trophoblast protein-1 (oTP-1) is the alpha-interferon (IFN alpha) variant, secreted by conceptuses and referred to as type I trophoblast interferon, that is responsible for maternal recognition of pregnancy in sheep. We have previously shown that oTP-1 is as potent an antiviral agent as any known IFN. IFNs also possess anticellular activity and are, in fact, used in cancer therapy and have been found to be effective in the treatment of cancer such as myelogenous and hairy cell leukemias. A significant problem with the currently used IFNs is the undesirable side effect of toxicity at high concentrations. In this study, we examined the anticellular activity and toxicity of oTP-1. It inhibited proliferation but did not exhibit toxicity at high concentrations, unlike known IFN alpha S. In an anticellular assay using colony formation of both the human amnionic line, WISH, and the bovine epithelial line, MDBK, oTP-1 inhibited both colony size and number. oTP-1 was as effective as human and bovine IFN alpha s on human and bovine cells, respectively; thus, it displays potent cross-species activity. Its activity was dose dependent, and inhibition of proliferation could be observed at concentrations as low as 1 unit/ml. Concentrations as high as 50,000 units/ml stopped proliferation, while viability was not impaired. Cell cycle analysis revealed an increased proportion of cells in S phase and a corresponding decreased proportion of cells in G2/M after 48 h of oTP-1 treatment. Therefore, oTP-1 appears to inhibit progress of cells through S phase. oTP-1 antiproliferative effects can be observed as early as 12 h after after the initiation of culture and are maintained through 6 days. Thus, oTP-1 exhibits potent anticellular activity without toxicity across species and may have therapeutic potential as an antitumor agent without the toxic effects generally associated with IFNs.