Advanced co-culture 3D breast cancer model to study cell death and nanodrug sensitivity of tumor spheroids

Abstract

The interaction between tumor cells and other cells in the tumor microenvironment (TME) dramatically affects the behavior and progression of the disease. Fibroblasts, as a major component of TME, play a role in cancer development and drug resistance. The current study demonstrates a microfluidic-based co-culture 3D breast cancer spheroids with simplified on-chip testing. To better mimic the breast TME, we have successfully generated a 3D stroma-rich in vitro model of breast cancer using fibroblasts and breast cancer cells. Using fluorescence imaging and histology techniques, the developed spheroids were characterized. MDA-MB-231 cells were successfully grown into 3D spheroids. Upon co-culturing the cells, a decrease in spheroid diameter was detected. Furthermore, tumor spheroids' overall viability was increased when co-cultured with fibroblasts over 5 days. The results demonstrated an increase in ECM content in co-culture spheroids (heterotypic spheroids) compared to mono-culture spheroids (homotypic spheroids), as demonstrated by the augmentation in the quantity of blue stain all over the spheroids. When exposed to liposomal doxorubicin nanodrug, a survival advantage was noticed in heterotypic spheroids compared to mono-culture spheroids (91 % vs. 82 %). The results highlighted the significance of using 3D tumor models rather than 2D systems as a realistic platform for proper evaluation of therapeutics efficacy. The co-culture tumor spheroids in proposed microwell-based microfluidic devices may be valuable to investigate TME and drug screening.