Objective To investigate the effect and mechanism of triptolide (TPL) on the expression of breast cancer susceptibility gene1 (BRCA1) in triple-negative breast cancer (TNBC) cells.
Methods TNBC cell line MDA-MB-468 carrying wild type BRCA1 gene was treated with different concentrations of TPL (12.5, 25, 50, and 100 nmol/L). The cell proliferation was detected with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; the expression of BRCA1, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) mRNA were measured with real-time reverse transcription PCR (RT-PCR); and the expression of BRCA1 and its phosphorylation, ATM, and ATR protein were measured with Western blot.
Results The growth of MDA-MB-468 cells was significantly inhibited after treated with TPL and the inhibition rate was concentration-dependent, with the inhibition rate of 13.3%, 32.3%, 42.9%, and 60.7% for the cells treated with 12.5, 25.0, 50.0, and 100 nmol/L TPL. Compared to those of the control group, the expressions of BRCA1, ATM, and ATR mRNA and the expressions of BRCA1, ATM, and ATR protein were significantly reduced after treated with TPL and the reductions were also concentration-dependent. In addition, TPL inhibited specifically the phosphorylation of BRCA1Ser-152 in a dose-response manner.
Conclusion TPL could induct the apoptosis of triple-negative breast cancer cell line MDA-MB-468, and the possible mechanism is the inhibition of BRCA1gene expression and the phosphorylation of the gene.
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