Objective  To observe the association between Notch1 expression and PAC sensitivity in breast cancer cells.

  Methods  The siRNA interference against Notch1 and endocellular Notch1 inhibitor, N-N-(3, 5-difluorophenacetyl)-1-alanyl -S-phenylglycine t-butyl lester (DAPT) were employed to down-regulate Notch1 activity and the inhibitory action was detected through Western blot and RT-PCR, respectively. After 24 hours of exposure to PAC at different concentrations (0, 1, 5, 10, 15, 20, 25 μg/mL), the cell viability of the control group and the experimental group was tested using the MTT colorimetric method, i.e., 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide). Immunohistochemistry (IHC) was used to observe the Notch1 expression in PAC-sensitive and non-sensitive cases, and collagen gel droplet embedded culture-drug sensitivity test (CD-DST) was carried out to determine the sensitivity of different cases to the PAC.

  Results  Down-regulation of Notch1 expression by Notch1 siRNA interference or inhibition of Notch1 activity by DAPT significantly increased the sensitivity of MDA-MB-231 cells to PAC (P < 0.05). In the IHC study, the Notch1 expression in PAC-sensitive cases was much lower than in non-sensitive cases (P < 0.01).

  Conclusion  The Notch1 expression significantly influences and negatively correlates with the sensitivity of breast cancer to PAC.