Biomedicine, School of Health Sciences, University of Skövde, 54145 Skövde, Sweden.
Int J Mol Sci. 2022 Jul 26;23(15):8237. doi: 10.3390/ijms23158237.
Digitoxin has repeatedly shown to have negative effects on cancer cell viability; however, the actual mechanism is still unknown. In this study, we investigated the effects of digitoxin (1-100 nM) in four pancreatic cancer cell lines, BxPC-3, CFPAC-1, Panc-1, and AsPC-1. The cell lines differ in their KRAS/BRAF mutational status and primary tumor or metastasis origin. We could detect differences in the basal rates of cell proliferation, glycolysis, and ROS production, giving the cell lines different phenotypes. Digitoxin treatment induced apoptosis in all four cell lines, but to different degrees. Cells derived from primary tumors (Panc-1 and BxPC-3) were highly proliferating with a high proportion of cells in the S/G2 phase, and were more sensitive to digitoxin treatment than the cell lines derived from metastases (CFPAC-1 and AsPC-1), with a high proportion of cells in G0/G1. In addition, the effects of digitoxin on the rate of glycolysis, ROS production, and proliferation were dependent on the basal metabolism and origin of the cells. The KRAS downstream signaling pathways were not altered by digitoxin treatment, thus the effects exerted by digitoxin were probably disconnected from these signaling pathways. We conclude that digitoxin is a promising treatment in highly proliferating pancreatic tumors.
地高辛已反复证明对癌细胞活力有负面影响；然而，其实际机制仍不清楚。在这项研究中，我们研究了地高辛（1-100 nM）对四种胰腺癌细胞系（BxPC-3、CFPAC-1、Panc-1 和 AsPC-1）的影响。这些细胞系在 KRAS/BRAF 突变状态和原发肿瘤或转移起源上存在差异。我们可以检测到细胞增殖、糖酵解和 ROS 产生的基础速率存在差异，使细胞系呈现不同的表型。地高辛处理诱导了所有四种细胞系的细胞凋亡，但程度不同。源自原发肿瘤（Panc-1 和 BxPC-3）的细胞增殖活跃，S/G2 期细胞比例较高，对地高辛处理比源自转移的细胞系（CFPAC-1 和 AsPC-1）更为敏感，G0/G1 期细胞比例较高。此外，地高辛对糖酵解、ROS 产生和增殖速率的影响取决于细胞的基础代谢和起源。地高辛处理并未改变 KRAS 下游信号通路，因此地高辛发挥的作用可能与这些信号通路无关。我们得出结论，地高辛是一种有前途的治疗高度增殖性胰腺肿瘤的方法。
