Inhibition of gamma-secretase in Notch1 signaling pathway as a novel treatment for ovarian cancer

Autor: Mengran Liu, Wandong Xu, Zhaoyi Feng, Chenguang Zhang, Hongwu Wen
Rok vydání: 2016
Předmět:
0301 basic medicine
Time Factors
Notch
endocrine system diseases
Antineoplastic Agents
Apoptosis
Kaplan-Meier Estimate
Carcinoma
Ovarian Epithelial
γ-secretase
03 medical and health sciences
0302 clinical medicine
Protein Domains
NICD
Cell Line
Tumor
Ovarian carcinoma
medicine
Humans
Protease Inhibitors
Neoplasms
Glandular and Epithelial
Receptor
Notch1
Gamma secretase
Cell Proliferation
Proportional Hazards Models
Cancer immunology
Ovarian Neoplasms
epithelial ovarian carcinoma
Dose-Response Relationship
Drug
business.industry
Cell growth
Cancer
Dipeptides
Middle Aged
medicine.disease
female genital diseases and pregnancy complications
030104 developmental biology
Jagged1
Oncology
030220 oncology & carcinogenesis
Cancer cell
Immunology
Cancer research
Female
Amyloid Precursor Protein Secretases
Ovarian cancer
business
Jagged-1 Protein
Signal Transduction
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Zhaoyi Feng 1, 2, * , Wandong Xu 1, * , Chenguang Zhang 3 , Mengran Liu 1 , Hongwu Wen 1 1 Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China 2 Center for Cancer Immunology and Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA 3 Department of Medical Genetics, Capital Medical University, Beijing 100069, China * Co-first author Correspondence to: Hongwu Wen, email: wenhongwu3184@sohu.com Keywords: epithelial ovarian carcinoma, Notch, Jagged1, NICD, γ-secretase Received: July 22, 2016 Accepted: November 07, 2016 Published: December 24, 2016 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.
Databáze: OpenAIRE
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