Matrix-free microfluidic 3D biomimetic chip for identifying type I collagen on doxorubicin treated MDA-MB-231 cell

Abstract

The development of drug resistance in breast cancer cells posed significant challenges that necessitate overcoming. Traditional two-dimensional cell research models failed to replicate the tumor microenvironment (TME) in vivo, thus necessitating the utilization of three-dimensional cell culture models for anti-cancer drug research. In this study, we utilized a matrix-free microfluidic three-dimensional (3D) biomimetic chip to generate uniformly sized and highly viable tumor cell spheroids, setting it apart from conventional matrix-based spheroid models. Simultaneously, these cell spheroids were accurately retrieved and embedded within type I collagen to establish the TME environment and further investigate the mechanism by which type I collagen influences doxorubicin resistance in breast cancer cells. The research findings demonstrated that type I collagen enhanced the doxorubicin resistance in breast cancer cells by upregulating the expression levels of Bcl-2, Bcl-XL, and MRP1 proteins. Additionally, the up-regulation of MRP1 is mediated through the ERK1/2 signaling pathway. In conclusion, we posited that this microfluidic biomimetic chip offered a novel and sophisticated platform for three-dimensional tumor research. This platform was expected to facilitate a more comprehensive elucidation of the pharmacokinetic properties of tumor cells within the extracellular matrix (ECM) in future studies, thereby enhancing the efficiency and accuracy of in vitro drug screening.