Metronomic doses and drug schematic combination response tested within microfluidic models for the treatment of breast cancer cells (JIMT-1).

Abstract

Low-dose metronomic (LDM) chemotherapy is an alternative to conventional chemotherapy and is the most common use of low-dose levels of traditional chemotherapeutics in patients. The selection of patients, drug dosages and dosing intervals in LDM is empirical. In this study we systematically examined the schedule-dependent interaction of drugs on a breast cancer cell line (BCC) cultured in Lab on a Chip (LOC) microdevices. The LDM studies were combined with cell staining in order to better characterize different cell stages and modes of cell death, including caspase-dependent apoptosis, caspase-independent cell death and autophagy-dependent cell death. Microscope images were examined using the Fiji plugin Trainable Weka Segmentation to analyze cell area in 7500 images showing different types of cell death modes. Paclitaxel combined with LDM chemotherapy demonstrated a reduction in the area covered by live cells. In contrast, there was an induction of high levels of cell death due to caspase-dependent apoptosis. Furthermore, the microdevice used in this study is also an attractive alternative for staining cells in order to characterize and study BCC growth and development in situ.