Feng Zhaoyi, Xu Wandong, Zhang Chenguang, Liu Mengran, Wen Hongwu
Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China.
Center for Cancer Immunology and Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Oncotarget. 2017 Jan 31;8(5):8215-8225. doi: 10.18632/oncotarget.14152.
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.
上皮性卵巢癌（EOC）是妇科癌症的主要死亡原因。大多数患者直到癌症处于晚期且预后较差时才被诊断出来。Notch1信号通路在EOC中发挥致癌作用。关于γ-分泌酶的酶活性以及γ-分泌酶抑制剂作用于癌细胞的机制的研究很少。在此，我们表明Jagged1和NICD在卵巢癌中高表达。Notch1通路中Notch1、Jagged1和NICD的表达与卵巢癌的预后无关。卵巢癌细胞系SKOV3、CAOV3和ES2中γ-分泌酶的酶活性显著高于正常卵巢上皮细胞系T29。DAPT（一种γ-分泌酶抑制剂）降低了γ-分泌酶的酶活性，抑制了卵巢癌细胞系的增殖，并增加了其凋亡。因此，γ-分泌酶抑制剂可能成为精准医学领域中一种极具前景的新型卵巢癌治疗策略。
