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.
Zang
Shaolei
S
Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Chen
Feng
F
Dai
Jianjian
J
Guo
Dongmei
D
Tse
William
W
Qu
Xun
X
Ma
Daoxin
D
Ji
Chunyan
C
D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1