Multi breast cells-on-a-chip: efficient screening biological platform for determination of selective breast cancer cell apoptosis

Abstract In this study, a multi breast cell-on-a-chip system was developed to recapitulate human-like breast cancer microenvironments by simultaneously co-culturing normal (MCF-10 A) and breast cancer cell lines (MCF-7 and MDA-MB-231) and to confirm the potential of plasma-activated PBS (P-PBS) containing various reactive oxygen species (ROS), as selective breast cancer remedial agent. The developed chip not only provided a 3D microenvironment supporting cell survival and interactions due to the use of gelatin as an extracellular matrix but also facilitated homogeneous growth and interactions between the different breast cell lines. Moreover, selective breast cancer apoptosis was investigated by real-time image analysis after treating cells with P-PBS on the developed chip; IC₅₀ values for MCF-7 and MDA-MB-231 were 390.50 and 600.75 μM, respectively. In addition, the breast cancer cell apoptosis pathway was found to be related to the ROS-activated intrinsic apoptosis pathway. The developed multi breast cells-on-a-chip platform could be used as a bio-platform that complements the limitations of existing in vitro models. The chip accurately reproduces cell-to-cell interactions by providing a tumor microenvironment based on the co-culture of heterogeneous cancer and normal cells and is expected to contribute meaningfully to breast cancer research and customized treatment development.