RNAi-mediated knockdown of Notch-1 leads to cell growth inhibition and enhanced chemosensitivity in human breast cancer.

Notch signaling plays a critical role in determining cell fate such as proliferation, differentiation, and apoptosis. Accumulating evidence indicates that aberrant Notch signaling has tumor-promoting function in breast cancer. We hypothesized that Notch signaling may be a potential therapeutic target for human breast cancer. To address this issue, we down-regulated the expression of the Notch-1 receptor by siRNA in human breast cancer cells. We found that the down-regulation of Notch-1 signaling caused cancer cell growth inhibition by apoptosis induction. The effect of the down-regulation of Notch-1 may be through the inactivation of NF-kappaB. In addition, the down-regulation of Notch-1 signaling increased chemosensitivity to doxorubicin and docetaxel. Our results suggested that Notch signaling may be a promising target for breast cancer treatment.