Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
Invest New Drugs. 2013 Aug;31(4):1087-94. doi: 10.1007/s10637-013-9984-1. Epub 2013 Jun 10.
Cardiac glycosides have a long history in the treatment of cardiac disease. However, several preclinical studies as well as two phase I studies have shown that cardenolides may also possess anticancer effects. The mechanisms of these anticancer effects may include intracellular decrease of K(+) and increase of Na(+) and Ca(2+); intracellular acidification; inhibition of IL-8 production and of the TNF-α/NF-κB pathway; inhibition of DNA topoisomerase II and activation of the Src kinase pathway. To date three cardiac glycosides have been developed for treatment of cancer and were tested in a phase 1 clinical trial to determine dose limiting toxicities and maximum tolerated dose. Future studies of this novel class of anticancer drugs are warranted to determine their possible role in cancer treatment.
强心苷在心脏疾病的治疗中有悠久的历史。然而，一些临床前研究以及两项 I 期研究表明，强心苷类化合物也可能具有抗癌作用。这些抗癌作用的机制可能包括细胞内 K(+)的减少和 Na(+)和 Ca(2+)的增加；细胞内酸化；抑制白细胞介素-8 的产生和 TNF-α/NF-κB 通路；抑制 DNA 拓扑异构酶 II 和激活Src 激酶通路。迄今为止，已有三种强心苷类化合物被开发用于癌症治疗，并在 I 期临床试验中进行了测试，以确定剂量限制毒性和最大耐受剂量。有必要对这一类新型抗癌药物进行进一步研究，以确定它们在癌症治疗中的可能作用。
