关键词: 三阴性乳腺癌, 鞣花酸, BRCA1, PARP1, MDA-MB-231细胞

Abstract: Objective To investigate the effects of ellagic acid（EA） on the biological behaviors of breast cancer susceptibility gene 1（BRCA1） silenced in triple negative breast cancer cell line MDA-MB-231 and its possible mechanism. Methods Different concentrations of EA （0 μg/mL，1 μg/mL， 5 μg/mL，10 μg/mL and 20 μg/mL） were used to treat MDA-MB-231 cells for 24 h，48 h and 72 h，respectively. The inhibition rate of proliferation were assessed by MTT assay and the IC₅₀ was calculated to select the optimal drug concentration. After transfecting BRCA1 siRNA into MDA-MB-231 cells，EA was applied at a final concentration of 5 μg/mL for 0 h，24 h，48 h，72 h，96 h，and cell proliferation was detected by MTT assay. Scratch assay was used to detect cell migration，Transwell chamber was used to detect cell migration and invasion，RT-qPCR and Western blot were used to detect the expression of PARP1 mRNA and protein. Results Different concentrations of EA had significant inhibitory effect on the proliferation of MDA-MB-231 cells at 24 h，48 h and 72 h，and IC₅₀ were 13.739 μg/mL，10.645 μg/mL，5.344 μg/mL，respectively. The OD value in siRNA+EA group was significantly lower than that of control group，EA group and negative control group（P<0.001）. The cell migration rate and the number of transmembrane cells in siRNA+EA group were lower than those of the other three groups（P<0.001），and the expression of PARP1 mRNA and protein in siRNA+EA group were also significantly lower than those of the other three groups（P<0.001）. Conclusions EA can inhibit the proliferation，migration and invasion of BRCA1 silenced MDA-MB-231 cells in vitro，and its mechanism may be related to related DNA repair pathway disorders.

Key words: Triple negative breast cancer, Ellagic acid, BRCA1, PARP1, MDA-MB-231 cell