BRCA1 mutated cells are less likely to undergo ROS-mediated apoptosis after exposure to eribulin and paclitaxel
BRCA1 mutated cells are less likely to undergo ROS-mediated apoptosis after exposure to eribulin and paclitaxel
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DOI：
10.15369/sujms.33.118
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
A. Sasaki;Y. Tsunoda;Yuriko Inoue
中科院分区：
文献类型：
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作者：
A. Sasaki;Y. Tsunoda;Yuriko Inoue
三阴性乳腺癌是BRCA1基因突变的高发区。在本实验中，我们检测了BRCA1突变的不同亚型乳腺癌和野生型BRCA细胞中是否存在未诱导凋亡的细胞。将BRCA1野生型(MDA-MB-231和BT-549)和突变(MDA-MB-436)BRCA1细胞暴露于抗癌药物中，检测氧化应激产生的活性氧(ROS)和膜联蛋白V(Annexin V)(细胞凋亡指标)水平。野生型MDA-MB-231细胞经淫羊藿素和紫杉醇处理后，ROS水平和Annexin V水平均升高。因此，氧化应激可能激活了导致细胞凋亡的途径。灯盏花素和紫杉醇作用于BT-549细胞后，细胞内ROS水平显著升高(P<0.05)。而膜联蛋白V的表达无明显变化。经BRCA1突变的MDA-MB-436细胞经淫羊藿素和紫杉醇处理后，ROS水平显著升高，Annexin V的表达水平无明显变化。这表明BRCA1野生型BT-549细胞和BRCA1沉默的MDA-MB-436细胞对ROS介导的细胞凋亡具有抵抗力。这些结果表明，在选择化疗组合之前，应调查BRCA1突变和细胞亚型，以便在临床实践中进行适当的选择。
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.