Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation.
Effects of agents that inhibit cellular iron incorporation on bladder cancer cell proliferation.
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DOI：
10.1182/blood.v82.5.1608.bloodjournal8251608
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发表时间：
1993-09
期刊：
影响因子：
20.3
通讯作者：
P. Seligman;R. B. Schleicher;G. Siriwardana;J. Domenico;E. Gelfand
中科院分区：
文献类型：
--
作者：
P. Seligman;R. B. Schleicher;G. Siriwardana;J. Domenico;E. Gelfand
干扰细胞铁 (Fe) 掺入的药物可抑制肿瘤细胞增殖，包括与转铁蛋白 (Tf) 结合的金属，例如镓 (Ga) 或铟 (In)，以及 Fe 螯合剂，例如去铁胺 (DFO)。硝酸镓可有效治疗转移性膀胱癌，并且这些患者表现出干扰铁代谢的证据。我们在此表明膀胱癌细胞体外增殖依赖于 Tf-Fe。即使在存在生理浓度的 Tf-Fe 的情况下，体内容易达到的 DFO 浓度也能抑制细胞增殖。 Tf-Ga 对增殖的抑制与细胞 Fe 掺入的减少有关。然而，当将生理浓度的Tf-Fe添加到等摩尔浓度的Tf-Ga时，尽管增殖受到抑制，但明显的Fe掺入是明显的。因此，除了干扰Fe掺入之外，Ga还可以干扰细胞内Fe分布和/或直接抑制细胞增殖所必需的Fe（或非Fe）需要过程。 DFO 随后依次添加 Tf-Ga 可显着增强增殖抑制作用。这种组合的作用似乎与干扰铁代谢和增加镓吸收有关。这种顺序组合可能有助于治疗膀胱癌。
Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe-) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.