Background
The Notch pathway is dysregulated in ovarian cancer. We sought to examine the role of Notch and gamma-secretase (GS) inhibition in ovarian cancer. Materials and
Conclusion
GS inhibition does not directly affect cellular proliferation in ovarian carcinoma, but Notch pathway blockade may result in angiogenic alterations that may be therapeutically important.
Methods
Established ovarian cancer cell lines were used. Quantitative polymerase chain reaction (qPCR) was used to determine the relative expression of Notch receptor and ligands. Effects of GS inhibition on proliferation, colony formation, and downstream effectors were examined via methylthiazole tetrazolium (MTT) and Matrigel assays, and qPCR, respectively. In vivo experiments with a GS inhibitor and cisplatin were conducted on nude mice. Tumors were examined for differences in microvessel density, proliferation, and apoptosis.
Results
Notch3 was the most up-regulated receptor. The ligands JAGGED1 and DELTA-LIKE4 were both up-regulated. GS inhibition did not affect cellular proliferation or anchorage-independent cell growth over placebo. The GS inhibitor Compound-E reduced microvessel density in vivo.