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Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2016 Mar 18; Vol. 10, pp. 1225-32. Date of Electronic Publication: 2016 Mar 18 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Cell Cycle drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Glycogen Synthase Kinase 3 beta metabolism
Humans
Indoles chemistry
Ovarian Neoplasms pathology
Protein Kinase Inhibitors chemistry
Pyridines chemistry
Structure-Activity Relationship
Tumor Cells, Cultured
Glycogen Synthase Kinase 3 beta antagonists & inhibitors
Indoles pharmacology
Ovarian Neoplasms drug therapy
Ovarian Neoplasms enzymology
Protein Kinase Inhibitors pharmacology
Pyridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 27051274
- Full Text :
- https://doi.org/10.2147/DDDT.S102506