BRCA1 mutated cells are less likely to undergo ROS-mediated apoptosis after exposure to eribulin and paclitaxel

Abstract

Triple negative breast cancer has a high frequency of BRCA1 gene mutations. In this experiment, we examined whether there are cells that are not led to apoptosis in different subtypes of breast cancer with poor prognosis with BRCA1 mutation and wild type BRCA cells. Cells with BRCA1 wild-type （ MDA-MB-231 and BT-549 ） or mutated （ MDA-MB-436 ） BRCA1 were exposed to anticancer drugs, and the levels of reactive oxygen species （ ROS ） produced by oxidative stress and Annexin V （ an index of apoptosis ） were examined. The wild-type MDA-MB-231 cells showed increased ROS levels and Annexin V after exposure to eribulin and paclitaxel. Hence, the pathway leading to apoptosis may be activated by oxidative stress. ROS levels in BT-549 cells were significantly increased after exposure to eribulin and paclitaxel. However, there was no change in Annexin V. BRCA1-mutated MDA-MB-436 cells showed significantly increased ROS levels after exposure to eribulin and paclitaxel and no change in the Annexin V levels. This suggests that BRCA1 wild-type BT-549 cells and BRCA1-muted MDA-MB-436 cells were resistant to ROS-mediated apoptosis. These results indicate that BRCA1 mutation and cell subtypes should be investigated prior to selecting the chemotherapy combination to enable appropriate selection in clinical practice.