Notch1 is downregulated in esophageal squamous cell carcinoma (p < 0.00001), Notch1 expression at high levels was detected in GC (p = 0.02) and CRC (p < 0.001), and no significant difference exists between PC and normal tissue (p = 0.76).
Taken together, our findings demonstrated that HtrA1 could inhibit pancreatic cancer cell growth via regulating Notch-1 expression, which implied that HtrA1 might be developed as a novel molecular target for pancreatic cancer therapy.
A mouse xenograft model of pancreatic cancer was established to determine the effect of Notch1 inhibition on the killing effect of gemcitabine in vivo.
More importantly, miR-223 governs GR-induced EMT in part due to down-regulation of its target Fbw7 and subsequent upregulation of Notch-1 in pancreatic cancer.
A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2), followed by examination of chemosensitivity to gemcitabine.
Using a pancreas cancer tissue microarray, we noted that Jagged1, Notch3 and Notch4 are overexpressed in pancreas tumors (26%, 84% and 31% respectively), whereas Notch1 is expressed in blood vessels.
This was accompanied by increased apoptosis and concomitant attenuation of Notch-1 and NF-kappaB and down-regulation of NF-kappaB downstream genes, such as matrix metalloproteinase-9 and vascular endothelial growth factor, resulting in the inhibition of pancreatic cancer cell invasion through the Matrigel.
These findings suggest that Notch-1 down-regulation, especially by genistein, could be a novel therapeutic approach for the treatment of pancreatic cancer.