Abstract
Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. Most patients are not diagnosed until the cancer is at an advanced stage with poor prognosis. Notch1 signaling pathway plays an oncogenic role in EOC. There have been few studies on enzymatic activity of γ-secretase and the mechanism of how γ-secretase inhibitor works on cancer cell. Here, we show that Jagged1 and NICD were highly expressed in ovarian carcinoma. The expressions of Notch1, Jagged1 and NICD in Notch1 pathway did not correlate with outcome in ovarian cancer. The enzymatic activity of γ-secretase in ovarian cancer cell lines SKOV3, CAOV3 and ES2 is significantly higher than in normal ovarian epithelial cell line T29. DAPT (a γ-secretase inhibitor) reduced the enzymatic activity of γ-secretase, inhibited the proliferation, and increased the apoptosis in ovarian cancer cell lines. Hence, γ-secretase inhibitor may become a highly promising novel therapeutic strategy against ovarian cancer in the field of precision medicine.
Highlights
Ovarian cancer is the most deadly gynaecological cancer, with approximately 200,000 new cases diagnosed globally each year and more than 150,000 deaths due to the disease annually [1]
Jagged1 and Notch intracellular domain (NICD) are highly expressed in ovarian carcinoma
The expression of NICD was greatly reduced in ovarian cancer cell lines after treatment with Notch1 siRNA
Summary
Ovarian cancer is the most deadly gynaecological cancer, with approximately 200,000 new cases diagnosed globally each year and more than 150,000 deaths due to the disease annually [1]. Epithelial ovarian cancer (EOC) accounts for 90 % of all ovarian cancers and typically presents in post-menopausal women [2]. The pathologic type of EOC includes clear cell carcinoma, mucinous carcinoma, endometrioid carcinoma, low-grade serous ovarian carcinoma and high-grade serous carcinoma [3]. Most patients are not diagnosed until the cancer is at an advanced stage. Standard treatment for EOC involves cytoreductive surgery followed by platinumbased chemotherapy. Recurrence is frequent (around 70%) and prognosis is globally poor [4]
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