Mechanical effects modulate drug resistance in MCF-7-derived organoids: Insights into the wnt/β-catenin pathway

Abstract

Addressing drug resistance poses a significant challenge in cancer treatment, as cancer cells develop diverse mechanisms to evade chemotherapy drugs, leading to treatment failure and disease relapse. Three-dimensional (3D) cell culture has emerged as a valuable model for studying drug resistance, although the underlying mechanisms remain elusive. By obtaining a better understanding of drug resistance within the 3D culture environment, we can develop more effective strategies to overcome it and improve the success of cancer treatments. Notably, the physical structure undergoes notable changes in 3D culture, with mechanical effects believed to play a pivotal role in drug resistance. Hence, our study aimed to explore the influence of mechanical effects on drug resistance by analyzing data related to "drug resistance" and "mechanobiology". Through this analysis, we identified β-catenin and JNK1 as potential factors, which were further examined in MCF-7 cells cultivated under both 2D and 3D culture conditions. Our findings demonstrate that β-catenin is activated through canonical and non-canonical pathways and associated with the drug resistance, particularly in organoids obtained under 3D culture.