Globig Philipp, Willumeit-Römer Regine, Martini Fernanda, Mazzoni Elisa, Luthringer-Feyerabend Bérengère J C
Institute of Metallic Biomaterials, Helmholtz-Zentrum Hereon, 21502, Geesthacht, Germany.
Department of Medical Sciences, University of Ferrara, 44121, Ferrara, Italy.
Bioact Mater. 2021 Dec 30;16:320-333. doi: 10.1016/j.bioactmat.2021.12.031. eCollection 2022 Oct.
Osteosarcoma is one of the most common cancers in young adults and is commonly treated using surgery and chemotherapy. During the past years, these therapy approaches improved but failed to ameliorate the outcomes. Therefore, novel, targeted therapeutic approaches should be established to enhance treatment success while preserving patient's quality of life. Recent studies suggest the application of degradable magnesium (Mg) alloys as orthopedic implants bearing a potential antitumor activity. Here, we examined the influence of Mg-based materials on an osteosarcoma-fibroblast coculture. Both, Mg and Mg-6Ag did not lead to tumor cell apoptosis at low degradation rates. Instead, the Mg-based materials induced cellular dormancy in the cancer cells indicated by a lower number of Ki-67 positive cancer cells and a higher p38 expression. This dormancy-like state could be reversed by reseeding on non-degrading glass slides but could not be provoked by inhibition of the protein kinase R-like endoplasmic reticulum kinase. By investigating the influence of the disjunct surface-near effects of the Mg degradation on cell proliferation, an increased pH was found to be a main initiator of Mg degradation-dependent tumor cell proliferation inhibition.
骨肉瘤是年轻成年人中最常见的癌症之一，通常采用手术和化疗进行治疗。在过去几年中，这些治疗方法有所改进，但未能改善治疗结果。因此，应建立新的靶向治疗方法，以提高治疗成功率，同时保持患者的生活质量。最近的研究表明，可降解镁（Mg）合金作为具有潜在抗肿瘤活性的骨科植入物具有应用前景。在此，我们研究了镁基材料对骨肉瘤-成纤维细胞共培养的影响。在低降解率下，镁和镁-6银均未导致肿瘤细胞凋亡。相反，镁基材料诱导癌细胞进入细胞休眠状态，表现为Ki-67阳性癌细胞数量减少和p38表达增加。这种类似休眠的状态可通过重新接种到非降解载玻片上而逆转，但不能通过抑制蛋白激酶R样内质网激酶来诱发。通过研究镁降解的不同表面附近效应对细胞增殖的影响，发现pH值升高是镁降解依赖性肿瘤细胞增殖抑制的主要启动因素。
