Lung cancer remains the leading cause of cancer mortality because of its metastatic potential and high malignancy. The discovery of new applications for old drugs is a shortcut for cancer therapy. We recently investigated the antitumour effect of digoxin, a well-established drug for treating heart failure, against nonsmall cell lung cancer A549 and H1299 cells. Digoxin inhibited the proliferation and colony-forming ability of the 2 cell lines and arrested the cell cycle at the G0/G1 phase in A549 cells and the G2/M phase in H1299 cells. Mitochondria-mediated apoptosis was induced in A549 cells but not in H1299 cells after treatment with digoxin. Moreover, digoxin inhibited the migration, invasion, adhesion and epithelial-mesenchymal transition of A549 and H1299 cells. Autophagy was induced in both cell lines after treatment with digoxin, with an increase in autophagosome foci. In addition, digoxin inhibited the phosphorylation of Akt, mTOR and p70S6K, signalling molecules of the PI3K/Akt pathway that are known to be involved in tumour cell survival, proliferation, metastasis and autophagy. Our findings suggest that digoxin has the potential to be used for therapy for human nonsmall cell lung cancer, but further evidence is required.

中文翻译：

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地高辛通过阻断 PI3K/Akt 通路对人类非小细胞肺癌细胞发挥抗癌活性。

肺癌由于其转移潜力和高恶性度，仍然是癌症死亡的主要原因。旧药新应用的发现是癌症治疗的捷径。我们最近研究了地高辛（一种成熟的治疗心力衰竭的药物）对非小细胞肺癌 A549 和 H1299 细胞的抗肿瘤作用。地高辛抑制2个细胞系的增殖和集落形成能力，在A549细胞的G0/G1期和H1299细胞的G2/M期阻滞细胞周期。用地高辛处理后，线粒体介导的细胞凋亡在 A549 细胞中被诱导，而在 H1299 细胞中则没有。此外，地高辛抑制A549和H1299细胞的迁移、侵袭、粘附和上皮间质转化。用地高辛处理后，两种细胞系均诱导自噬，随着自噬体病灶的增加。此外，地高辛抑制 Akt、mTOR 和 p70S6K 的磷酸化，这些信号分子是已知参与肿瘤细胞存活、增殖、转移和自噬的 PI3K/Akt 通路的信号分子。我们的研究结果表明，地高辛有可能用于治疗人类非小细胞肺癌，但需要进一步的证据。