Drug Design, Development and Therapy (Mar 2016)
Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
Abstract
Shuo Chen, Kai-Xuan Sun, Miao-Xiao Feng, Xiu-Bo Sang, Bo-Liang Liu, Yang Zhao Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Background: Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3β inhibitor AZD1080 in ovarian cancer cell lines. Methods: A2780 and OVCAR3 ovarian cancer cell lines were exposed to AZD1080, after which cell proliferation, cell cycle, invasion, and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction and Western blot were used to assess the respective mRNA and protein expression levels of GSK-3β, CDK2, CDK1, cyclin D1, matrix metalloproteinase-9 (MMP9), and Bcl-xL. Results: AZD1080 exposure suppressed ovarian cancer cell proliferation, invasion, migration, and lamellipodia formation, and induced G1 arrest, which was concentration dependent. AZD1080 also significantly downregulated GSK-3β, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at both mRNA and protein levels. Conclusion: Taken together, our results demonstrate that the GSK-3β inhibitor AZD1080 suppresses ovarian cancer development and therefore may indicate a new direction for ovarian cancer treatment. Keywords: ovarian cancer, GSK-3β inhibitor, AZD1080, tumorigenesis, progression
