(573a) Low Doses of Paclitaxel Induce a Dormant State in Brain Metastatic Breast Cancer Spheroids
AIChE Annual Meeting
Wednesday, November 16, 2022 - 3:30pm to 3:49pm
In this study, we demonstrate that brain metastatic breast cancer (BMBC) spheroids are able to survive low doses of chemotherapy drug paclitaxel by exhibiting a dormant state through upregulation of phosphorylated p38 (p-p38). 10,000 MDA-MB-231Br BMBC cells were utilized to prepare spheroids. Spheroids were cultured in different drug concentrations (ranging from 0 to 100 µM) for a period of 7 days. Our results demonstrated that the cross-sectional area of the spheroids cultured in 80 nM paclitaxel remained constant throughout the culture time. We observed a decrease in spheroid areas for drug concentrations > 80 nM. 80 nM paclitaxel treated spheroids contained lower levels of proliferating cells than the control spheroids as demonstrated via Ki67 and EdU staining. The percentage of apoptotic cells increased with increase in drug dosages. We investigated the ratio of % extracellular signal - regulated kinase 1/2 (p-ERK) to % p-p38 positive cells as low ratio of p-ERK to p-p38 has been reported to be a characteristic of the dormant state. The ratio of % p-ERK: % p-p38 positive cells were higher in untreated spheroids compared to 80 nM paclitaxel treated spheroids. In addition, 80 nM paclitaxel treated spheroids attained growth upon the withdrawal of drug demonstrating reversibility of the dormant state. Overall, these results providing insight into regulation of the dormant state mediated via low dose chemotherapy.