Tumor Biology

, Volume 37, Issue 4, pp 4857–4864 | Cite as

Effects of the GSK-3β inhibitor (2Z,3E)-6-bromoindirubin-3′-oxime upon ovarian cancer cells

  • Ai-Song Yu
  • Lin Zhao
Original Article


Ovarian cancer (OC) is a deadly disease, and despite improvements in treatment, overall 5-year survival is low. Glycogen synthase kinase (GSK)-3β is a multifunctional serine/threonine kinase. We wished to ascertain if the GSK-3β inhibitor (2Z,3E)-6-bromoindirubin-3′-oxime, known as “BIO,” can suppress OC development. The OC cell lines A2780 and OVCAR3 were exposed to BIO. At different time points, cell proliferation, apoptosis, cell cycle, and cell invasion/cell migration assays were carried out. Phalloidin staining was undertaken to observe lamellipodia formation. Real-time reverse transcription-polymerase chain reaction and western blotting were used to assess expression of messenger RNA (mRNA) and protein of GSK-3β, cyclin D1, matrix metalloproteinase (MMP)-9, and p21. BIO suppressed the proliferation, invasion, and migration of OC cells; reduced lamellipodia formation; and induced G1 arrest of the cell cycle. BIO exposure led to a significant downregulation of mRNA and protein expression of cyclin D1 and MMP9 in comparison with untreated control cells. In contrast, BIO exposure upregulated mRNA and protein expression of p21 in comparison with untreated control cells. Besides, GSK-3β small interfering RNA (siRNA) transfection in ovarian cancer cells also downregulated GSK-3β, cyclin D1, and MMP9 protein expression while upregulated p21 expression. These data suggest that BIO, as an inhibitor of GSK-3β, can suppress OC development. Therefore, BIO could be a candidate drug for the treatment of OC.


Ovarian cancer Glycogen synthase kinase-3β Proliferation Migration Invasion 


Compliance with ethical standards

Conflicts of interest


Authors’ contributions

LZ conceived the study and analyzed interpretation. AS Y and LZ carried out the experiments, analyzed the data, and wrote the first and final draft of the manuscript. All authors read and approved the final manuscript.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Preventive Medicine, School of Public HealthDalian Medical UniversityDalianChina
  2. 2.Department of Breast SurgeryLiaoning Cancer Hospital & InstituteShenyangChina
  3. 3.Clinical Oncology CollegeDalian Medical UniversityShenyangChina

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