Three-dimensional cell culture models for metallodrug testing: induction of apoptosis and phenotypic reversion of breast cancer cells by the trans-[Ru(PPh3)2(N,N-dimethyl-N-thiophenylthioureato-k2O,S)(bipy)]PF6 complex

摘要: Many studies have revealed the advantages of using three-dimensional (3D) culture over traditional two-dimensional (2D) monolayer techniques. The 3D cell models represent biologically relevant approaches to better mimic tumor organization observed in vivo. These high potential for anticancer drug development and screening, which challenges include resistance treatment risk toxicity patients. candidates do not reach clinical trials as they fail preclinical tests vivo, although were promising 2D cultures. Models from cultures are proposed intermediate screening filters between vivo assays. It has been suggested that ruthenium complexes great breast cancer treatment. Here, we tested trans-[Ru(PPh3)2(N,N-dimethyl-N-thiophenylthioureato-k2O,S)(bipy)]PF6 complex lines different techniques, including embedded, ‘on top’ disease-on-a-chip (DOC) reproduce physical aspects microenvironment. had pronounced but distinct cytotoxic effects on tumors cultured collagen I appropriate stiffness disease stage; extent induced apoptosis depends preinvasive (S2 cells) invasive (T4-2 MDA-MB-231 nature triple-negative models. Remarkably, DOC model, simulates ductal architecture, was T4-2 no remarkable effect differentiated luminal epithelial S1 cells, demonstrating selectivity against cells. In addition, a lower concentration abrogated malignant phenotype cells with reduction EGFR, p50 NFκB, β1-integrin expression. To best our knowledge, this work uniquely demonstrates induction phenotypic reversion results warrant moving evaluation complex.