Low dose chemotherapy induces a dormant state in brain metastatic breast cancer spheroids

Surviving breast cancer cells post chemotherapy, metastasize, and develop recurrent tumors at distant organs. These cells are known to exhibit a dormant phenotype at metastatic sites and survive for extended periods of time. The mechanisms involved in attaining dormancy are unclear, including how chemotherapeutic drugs influence this state. Herein, we investigated the impact of a chemotherapy drug, paclitaxel, on brain metastatic breast cancer spheroids by culturing them in different drug concentrations for a period of 7 days. Our results demonstrated that spheroids survive lower doses (80 nM) of chemotherapy by exhibiting a dormant state and low levels of proliferation as characterized via Ki67 and EdU staining, as well as p-p38 and p-ERK, known markers of dormancy and proliferation. Upon withdrawal of drug, dormant spheroids attained growth indicating that the observed dormant state was reversible. Overall, these results provide insight into regulation of the dormant state mediated via low dose chemotherapy.