Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Oncol Rep. 2010 Apr;23(4):893-9. doi: 10.3892/or_00000712.
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.
Notch 信号通路在决定细胞命运（如增殖、分化和凋亡）方面起着关键作用。越来越多的证据表明，异常的 Notch 信号通路在乳腺癌中具有促进肿瘤的功能。我们假设 Notch 信号通路可能是人类乳腺癌的一个潜在治疗靶点。为了解决这个问题，我们通过 siRNA 下调了人乳腺癌细胞中 Notch-1 受体的表达。我们发现 Notch-1 信号通路的下调通过诱导细胞凋亡导致癌细胞生长抑制。下调 Notch-1 的作用可能是通过 NF-κB 的失活来实现的。此外，下调 Notch-1 信号通路增加了对阿霉素和多西紫杉醇的化疗敏感性。我们的结果表明，Notch 信号通路可能是治疗乳腺癌的一个有前途的靶点。
