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 recurrin...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)wirebased 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.展开更多
基金the National Key Research and Development Program of China(2018YFC1106600)the Interdisciplinary Program of Shanghai Jiao Tong University(ZH2018QNB07)。
文摘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)wirebased 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.
