LAUSR

Relapse and metastasis of tumor may occur for osteosarcoma (OS) patients after clinical resection. Conventional metallic scaffolds provide sufficient mechanical support to the defected bone but fail to eradicate recurring tumors. Here we report that biodegradable magnesium (Mg) wire-based implant can inhibit OS growth. In brief, the Mg wires release Mg ions to activate the transport of zinc finger protein Snail1 from cytoplasm to cell nucleus, which induces apoptosis and inhibits proliferation of OS cells through a parallel antitumor signaling pathway of miRNA-181d-5p/TIMP3 and miRNA-181c-5p/NLK downstream. Simultaneously, the hydrogen gas evolution from Mg wires eliminates intracellular excessive reactive oxygen species, by which the growth of bone tumor cells is suppressed. The subcutaneous tumor-bearing experiment of OS cells in nude mice further confirms that Mg wires can effectively inhibit the growth of tumors and prolong the survival of tumor-bearing mice. In addition, Mg wires have no toxicity to normal cells and tissues. These results suggest that Mg implant is a potential anti-tumor scaffold for OS patients. 骨癌患者切除术后可能发生复发和转移. 传统的金属支架可 以对骨缺损部位提供力学支撑, 但无法有效清除复发的肿瘤细胞. 本文中, 我们介绍了一种可以抑制骨肉瘤生长的生物可降解镁丝 植入物. 简而言之, 镁丝释放镁离子激活锌指蛋白Snail1从胞浆到 细胞核的转运, 通过下游的miRNA-181d-5p/TIMP3和miRNA-181c-5p/NLK两条平行的抗肿瘤信号通路诱导骨肉瘤细胞凋亡, 抑 制骨肉瘤细胞增殖. 同时, 镁丝释放出的氢气消除了细胞内过多的 活性氧, 从而抑制了骨肿瘤细胞的生长. 裸鼠骨肉瘤细胞皮下荷瘤 实验进一步证实镁丝能有效抑制肿瘤生长, 延长荷瘤小鼠生存期. 此外, 镁丝对正常细胞和组织无毒性, 揭示了镁植入物是骨肉瘤患 者潜在的抗肿瘤支架材料.