Department of Orthopedics, Jining No.1 People's Hospital, Jining, China.
Department of Interventional Radiology, Jining No.1 People's Hospital, Jining, China.
J Orthop Surg Res. 2020 Feb 19;15(1):57. doi: 10.1186/s13018-020-01585-x.
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.
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.
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.
骨肉瘤患者血液和肿瘤组织中的锌含量及其调控和分子机制尚未见报道。
本研究表明，骨肉瘤患者血液和肿瘤组织中的锌含量明显降低。CCK-8 和 Transwell 室分析显示，锌处理显著抑制骨肉瘤细胞的增殖和侵袭能力。Western blot 分析表明，锌显著增加了 caspase-3 和 caspase-9 的表达水平，提示锌抑制了骨肉瘤细胞的生长并促进了其凋亡。此外，锌干预后骨肉瘤细胞中 Wnt-3a 和 β-连环蛋白（Wnt/β-连环蛋白信号通路的标志物蛋白）的表达水平明显增加，表明该通路明显被激活。然而，当用 XAV939（Wnt 拮抗剂）抑制 Wnt/β-连环蛋白信号通路时，锌对骨肉瘤细胞凋亡、增殖和侵袭能力的影响被逆转。
本研究首次报道了骨肉瘤患者血液和肿瘤组织中锌水平的变化，并初步验证了锌通过诱导 Wnt/β-连环蛋白信号通路抑制骨肉瘤细胞的增殖和侵袭，促进其凋亡，从而抑制肿瘤生长。
