Although there are many therapeutic strategies such as surgery and chemotherapy, the prognosis of osteosarcoma (OS) is still far from being satisfactory. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. In the present study, we investigated the anti-OS activity of Alantolactone (ALT), a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium, and probed the possible mechanism involved. We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells. Then, we validated that ALT reduced migration, decreased invasion possibly through reversing epithelial mesenchymal transition (EMT) process and suppressing Matrix metalloproteinases (MMPs). Moreover, we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro. In addition, we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo. Mechanistically, ALT inhibited the activity of Wnt/β-catenin and p38, ERK1/2 and JNK Mitogen Activated Protein Kinases (MAPKs) signal pathway. Notably, the combination of ALT and Wnt/β-catenin inhibitor, as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation, migration and invasion of OS cells. Collectively, our results validate the ALT may inhibit proliferation, metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.

尽管有手术和化疗等多种治疗策略，但骨肉瘤（osteosarcoma，OS）的预后仍远不尽如人意。开发更有效、耐受性更好、更安全的OS治疗药物迫在眉睫。在本研究中，我们研究了木香内酯 (ALT) 的抗 OS 活性，ALT 是一种主要存在于旋覆花中的天然桉树倍半萜内酯，并探讨了可能的机制。我们证明 ALT 显着抑制各种人类 OS 细胞系的细胞增殖，同时对正常细胞具有相对较低的细胞毒性。然后，我们验证了 ALT 可能通过逆转上皮间充质转化 (EMT) 过程和抑制基质金属蛋白酶 (MMP) 来减少迁移、减少侵袭。而且，体外。此外，我们在体内异种移植模型中证实 ALT 抑制了 OS 143 细胞的肿瘤生长和转移。从机制上讲，ALT 抑制 Wnt/β-catenin 和 p38、ERK1/2 和 JNK 丝裂原活化蛋白激酶 (MAPKs) 信号通路的活性。值得注意的是，ALT 和 Wnt/β-catenin 抑制剂的组合，以及 ALT 和 MAPKs 抑制剂的组合对抑制 OS 细胞的增殖、迁移和侵袭产生协同作用。总的来说，我们的结果证实 ALT 可能通过抑制 Wnt/β-Catenin 和 MAPKs 信号通路来抑制人类 OS 细胞的增殖、转移并促进细胞凋亡。