Moran P L, Seligman P A
University of Colorado Health Sciences Center, Denver 80262.
Cancer Res. 1989 Aug 1;49(15):4237-41.
In previous studies, we have demonstrated that transferrin-gallium inhibits cellular proliferation by a mechanism whereby cellular iron utilization is impaired. Since indium, a similar class 3A metal, has not been well studied, we examined its effects on cellular iron uptake and cellular proliferation. In these studies, we provide evidence that indium, when bound to transferrin, has a 50-fold higher effect on inhibition of cellular proliferation than indium added as indium salt. Cells exposed to relatively low concentrations of transferrin-indium exhibit markedly increased transferrin receptor expression but, as with transferrin-gallium, these cells incorporate an inappropriately low amount of iron, suggesting that there is a defect in the release of internalized iron from transferrin. In further studies, we utilize a monoclonal antibody against transferrin receptor that inhibits transferrin-mediated iron uptake. This antibody exhibits a dose-related inhibition of cellular proliferation, and when both transferrin-indium and monoclonal antibody are added to media, there is a more than additive effect on inhibition of cellular proliferation.
在先前的研究中，我们已经证明转铁蛋白-镓通过损害细胞铁利用的机制来抑制细胞增殖。由于铟，一种类似的3A类金属，尚未得到充分研究，我们研究了其对细胞铁摄取和细胞增殖的影响。在这些研究中，我们提供证据表明，与转铁蛋白结合的铟对细胞增殖的抑制作用比以铟盐形式添加的铟高50倍。暴露于相对低浓度转铁蛋白-铟的细胞表现出转铁蛋白受体表达明显增加，但与转铁蛋白-镓一样，这些细胞摄取的铁量不适当低，这表明内化铁从转铁蛋白的释放存在缺陷。在进一步的研究中，我们使用了一种针对转铁蛋白受体的单克隆抗体，该抗体可抑制转铁蛋白介导的铁摄取。这种抗体表现出与剂量相关的细胞增殖抑制作用，当将转铁蛋白-铟和单克隆抗体都添加到培养基中时，对细胞增殖的抑制作用具有超过相加的效果。
