The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Sci Rep. 2020 Oct 22;10(1):18034. doi: 10.1038/s41598-020-75142-1.
Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug's harmful side effects.
胺碘酮是一种抗心律失常药物，于 1985 年获得美国食品和药物管理局（FDA）批准。临床前研究表明，胺碘酮可诱导多种类型的癌细胞产生细胞毒性，因此使其成为一种有潜力的抗癌治疗候选药物。然而，它也已知会引起多种严重的副作用。我们假设，除了在癌细胞中观察到的细胞毒性作用外，胺碘酮还对血管生成有间接影响，血管生成是肿瘤微环境中的一个关键因素。在这项研究中，我们研究了胺碘酮对由 U-87 MG 胶质母细胞瘤（GBM）细胞组成的小鼠肿瘤模型的影响，已知这些细胞会形成高度血管化的肿瘤。我们使用肿瘤和内皮细胞进行了几项体外检测，同时还使用了三种小鼠模型进行了体内检测。低剂量的胺碘酮显著缩小了 GBM 异种移植肿瘤的大小，并显示出强烈的抗血管生成作用，提示具有双重抗癌特性。我们的研究结果为进一步研究胺碘酮作为一种潜在的临床药物奠定了基础，在使用安全剂量时，胺碘酮既能保持其双重特性，又能避免药物的有害副作用。
