Investigating the effects of substrate stiffness on half-maximal inhibitory concentration of chemical anticancer drugs, cell viability and migration of cell lines

Cells are related to the extracellular matrix (ECM) via integrin and feel varying amounts of stiffness caused by various tissues, which can influence cancer cell treatment and control. Improving cancer treatment tactics requires understanding how substrate stiffness affects cancer cell behavior and how they respond to therapy. One of the most important novelties of this study is the investigation of drug concentrations on cancer cells cultured on substrates with different elastic modulus. Another novelty of this study is the investigation of the effects of anti-cancer drugs targeting the skeletal structure of cancer cells in contact with ECMs with different elastic moduli. In the present study, assays were used to investigate the effects of the elastic modulus of different ECMs on the treatment of cells. First, the effect of different drug concentrations on cancer cells cultured on different substrates was investigated with MTT assay, and then tests were performed to evaluate cell viability, migration, and gene expression of cultured cells on different substrates. The results show that substrate stiffness significantly affects drug response, with soft substrates showing higher levels of cytotoxicity, induction of apoptosis, and antimetastatic properties when compared to medium and stiff substrates. Furthermore, changes in apoptotic gene expression point to a mechanistic relationship between drug response, cellular fate determination, and substrate stiffness. These findings highlight the importance of using biomechanical cues in cancer therapy strategies and point to the possibility of using substrate stiffness as a target for therapeutic intervention and a prognosis marker.