Fluid Shear Stress Modulates Epithelial–Mesenchymal Transition and Drug Resistance in 3D Cancer Models

Abstract This study employs silk fibroin (SF)-coated microfluidic platforms to model three-dimensional (3D) tumor structures under fluid shear stress (FSS) and examines the impact of dynamic versus static culture conditions on gene expression and drug resistance in MCF-7 breast cancer cells. Specifically, we have assessed the expression of EpCAM and CK-18, alongside cellular responses to doxorubicin and docetaxel, with a focus on changes in MDR-1 and BCRP expression. Our findings indicate that dynamic culture conditions lead to a modest increase in EpCAM and a trend toward reduced CK-18 expression, potentially suggesting an early shift toward an epithelial–mesenchymal transition (EMT)-like phenotype, whereas static 3D conditions reveal higher CK-18 levels, indicative of an organized epithelial structure. Drug-response assays have showed a dose-dependent reduction in cell viability under FSS, accompanied by directional changes in MDR-1 and BCRP expression. In contrast, under static conditions, gene expression patterns are variable, potentially limiting their utility for drug resistance research. These findings underscore the importance of selecting culture systems that recapitulate in vivo conditions, providing valuable insights into cancer behavior and therapeutic response.