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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Digoxin And Other Cardiac Glycosides Inhibit Hif-1α Synthesis And Block Tumor Growth
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Digoxin And Other Cardiac Glycosides Inhibit Hif-1α Synthesis And Block Tumor Growth

机译：地高辛和其他心脏糖苷抑制Hif-1α合成并阻止肿瘤生长

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摘要

A library of drugs that are in clinical trials or use was screened for inhibitors of hypoxia-inducible factor 1 (HIF-1). Twenty drugs inhibited HIF-1-dependent gene transcription by >88% at a concentration of 0.4 μM. Eleven of these drugs were cardiac glycosides, including digoxin, ouabain, and proscillaridin A, which inhibited HIF-1α protein synthesis and expression of HIF-1 target genes in cancer cells. Digoxin administration increased latency and decreased growth of tumor xenografts, whereas treatment of established tumors resulted in growth arrest within one week. Enforced expression of HIF-1α by transfection was not inhibited by digoxin, and xenografts derived from these cells were resistant to the anti-tumor effects of digoxin, demonstrating that HIF-1 is a critical target of digoxin for cancer therapy.
机译：筛选了在临床试验或使用中的药物库中的缺氧诱导因子1（HIF-1）抑制剂。在0.4μM的浓度下，有二十种药物抑制HIF-1依赖性基因的转录> 88％。这些药物中有11种是强心苷，包括地高辛，哇巴因和螺旋藻苷A，它们抑制癌细胞中HIF-1α蛋白的合成和HIF-1靶基因的表达。地高辛的使用增加了潜伏期并减少了异种肿瘤的生长，而对已建立的肿瘤的治疗导致生长在一周之内停止。地高辛不会抑制通过转染增强的HIF-1α表达，并且源自这些细胞的异种移植物对地高辛的抗肿瘤作用具有抗性，表明HIF-1是地高辛在癌症治疗中的重要靶标。

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