骨肉瘤（OS）是一种高度侵略性的恶性骨肿瘤，主要发生在青少年。目前，化疗是临床实践中治疗OS最常用的方法。然而，由于药物耐受性、毒性和长期副作用，化疗并不能总是为OS患者，尤其是那些发生转移和复发的患者提供足够的益处。自然产物长期以来一直是抗肿瘤药物开发的优秀来源。在当前研究中，我们评估了甘草根和根茎中一种天然活性成分Echinatin（Ecn）的抗OS活性，并探讨了可能的机制。我们发现Ecn抑制人类OS细胞的增殖并阻断了S期细胞周期。此外，Ecn抑制了人类OS细胞的迁移和侵袭，同时诱导了其凋亡。然而，Ecn对正常细胞的细胞毒性较小。此外，Ecn抑制了OS细胞的异种移植肿瘤生长。从机制上讲，Ecn失活了Wnt/β-catenin信号通路，同时激活了p38信号通路。β-catenin的过表达和p38抑制剂SB203580都减弱了Ecn对OS细胞的抑制作用。值得注意的是，我们证明Ecn在体内外与顺铂（DDP）表现出协同抑制作用。因此，我们的结果表明Ecn可能通过调节Wnt/β-catenin和p38信号通路至少部分发挥抗OS作用。最有意义的是，所获得的结果提供了一种潜在的策略，通过与Ecn组合以改善DDP对OS细胞的杀瘤作用。版权所有©2023作者。由Elsevier Ltd.出版。保留所有权利。

Osteosarcoma (OS) is a highly aggressive malignant bone tumor that mainly occurs in adolescents. At present, chemotherapy is the most commonly used method in clinical practice to treat OS. However, due to drug resistance, toxicity and long-term side effects, chemotherapy can't always provide sufficient benefits for OS patients, especially those with metastasis and recurrence. Natural products have long been an excellent source of anti-tumor drug development. In the current study, we evaluated the anti-OS activity of Echinatin (Ecn), a natural active component from the roots and rhizomes of licorice, and explored the possible mechanism. We found that Ecn inhibited the proliferation of human OS cells and blocked cell cycle at S phase. In addition, Ecn suppressed the migration and invasion, while induced the apoptosis of human OS cells. However, Ecn had less cytotoxicity against normal cells. Moreover, Ecn inhibited the xenograft tumor growth of OS cells in vivo. Mechanistically, Ecn inactivated Wnt/β-catenin signaling pathway while activated p38 signaling pathway. β-catenin over-expression and the p38 inhibitor SB203580 both attenuated the inhibitory effect of Ecn on OS cells. Notably, we demonstrated that Ecn exhibited synergistic inhibitory effect with cisplatin (DDP) on OS cells in vitro and in vivo. Therefore, our results suggest that Ecn may exert anti-OS effects at least partly through regulating Wnt/β-catenin and p38 signaling pathways. Most meaningfully, the results obtained suggest a potential strategy to improve the DDP-induced tumor-killing effect on OS cells by combining with Ecn.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.