BACKGROUND The zinc content in the blood and tumor tissues of patients with osteosarcoma and the underlying regulation and molecular mechanism of zinc have not been reported. METHODS AND RESULTS This study showed that the zinc content in the blood and tumor tissues of patients with osteosarcoma significantly reduced. CCK-8 and Transwell chamber assays revealed that zinc treatment significantly inhibited the proliferation and invasion abilities of osteosarcoma cells. Western blot analysis indicated that the expression levels of caspase-3 and caspase-9 were significantly increased, suggesting that zinc inhibited the growth and promoted the apoptosis of osteosarcoma cells. In addition, the expression levels of Wnt-3a and β-catenin, the marker proteins of the Wnt/β-catenin signaling pathways, were significantly increased in osteosarcoma cells after zinc intervention, which demonstrated that the pathway was clearly activated. However, the effect of zinc on the apoptosis, proliferation, and invasion abilities of osteosarcoma cells was reversed when the Wnt/β-catenin signaling pathways was inhibited by XAV939 (Wnt antagonist) treatment. CONCLUSIONS This study is the first to report the changes in zinc levels in the blood and tumor tissues of patients with osteosarcoma and to preliminarily verify that zinc inhibits the proliferation and invasion and promote the apoptosis of osteosarcoma cells by inducing the Wnt/β-catenin signaling pathway, which ultimately inhibit cancer growth.

中文翻译：

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锌通过激活骨肉瘤中的Wnt-3a /β-catenin信号通路来促进细胞凋亡。

背景技术尚未报道骨肉瘤患者血液和肿瘤组织中的锌含量以及锌的潜在调节和分子机制。方法与结果本研究表明，骨肉瘤患者血液和肿瘤组织中的锌含量显着降低。CCK-8和Transwell室分析表明锌处理显着抑制了骨肉瘤细胞的增殖和侵袭能力。Western blot分析表明，caspase-3和caspase-9的表达水平明显升高，提示锌抑制了骨肉瘤细胞的生长并促进了其凋亡。另外，Wnt /β-catenin信号通路的标志蛋白Wnt-3a和β-catenin的表达水平，锌干预后，骨肉瘤细胞中的TNF-α显着增加，这表明该途径明显被激活。然而，当通过XAV939（Wnt拮抗剂）治疗抑制Wnt /β-catenin信号通路时，锌对骨肉瘤细胞凋亡，增殖和侵袭能力的作用被逆转。结论本研究首次报道骨肉瘤患者血液和肿瘤组织中锌水平的变化，并初步证实锌通过诱导Wnt /β-catenin信号传导抑制骨肉瘤细胞的增殖和侵袭并促进其凋亡。最终抑制癌症生长的途径。当通过XAV939（Wnt拮抗剂）抑制Wnt /β-catenin信号通路时，骨肉瘤细胞的侵袭能力逆转。结论本研究首次报道骨肉瘤患者血液和肿瘤组织中锌水平的变化，并初步证实锌通过诱导Wnt /β-catenin信号传导抑制骨肉瘤细胞的增殖和侵袭并促进其凋亡。最终抑制癌症生长的途径。当通过XAV939（Wnt拮抗剂）抑制Wnt /β-catenin信号通路时，骨肉瘤细胞的侵袭能力逆转。结论本研究首次报道骨肉瘤患者血液和肿瘤组织中锌水平的变化，并初步证实锌通过诱导Wnt /β-catenin信号传导抑制骨肉瘤细胞的增殖和侵袭并促进其凋亡。最终抑制癌症生长的途径。