Targeted inhibition of Notch1 gene enhances the killing effects of Paclitaxel on triple-negative breast cancer cells

Objective: To study the influence of targeted inhibition of Notchl gene on the killing effects of Paclitaxel on triple-negative breast cancer cells. Methods: The triple-negative [estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (Her2)] breast cancer cell line MDA-MB-231 and ER/PR/HER-2-positive breast cancer cell line MCF-7 were cultured, transfected with Notchl-siRNA-overexpression plasmid and blank plasmid, and treated with different concentrations of paclitaxel. and then the cell proliferation activity and apoptosis rate as well as the mRNA expression of Caspase-3. Caspase-9 and Bel-2 were determined. Results: Paclitaxel could decrease the MDA-MB-231 and MCF-7 cell proliferation activity as well as Bcl-2 mRNA expression, and increase MDA-MB-231 and MCF-7 cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression in dose dependent manners; with the same dose of paclitaxel treatment, the inhibitory effects on MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression as well as the promoting effects on MDA-MB-231 cell apoptosis and mRNA expression of Caspase-3 and Caspase-9 were weaker than those on MCF-7 cell; after 0.5 pM paclitaxel combined with Notchl-siRNA treatment, MDA-MB-231 cell proliferation activity and Bcl-2 mRNA expression were significantly lower than those after 0.5 pM paclitaxel combined with control plasmid treatment while cell apoptosis rate and inRNA expression of Caspase-3 and Caspase-9 were higher than those after 0.5 mu M paclitaxel combined with control plasmid treatment. Conclusions: Targeted inhibition of Notchl gene may enhance the killing effects of paclitaxel on triple-negative breast cancer cells by up-regulating the expression of Caspasc-3 and Caspase-9 and inhibiting the expression of Bcl-2.