Slow degrading Mg-based materials induce tumor cell dormancy on an osteosarcoma-fibroblast coculture model

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.