WITHDRAWN: Metformin antagonizes MPS-1-mediated IL-6/Stat3 signaling in ovarian cancer cells: possible mechanisms of stemness and angiogenesis inhibition

Abstract

To unveil the potential antitumor effects of metformin against ovarian cancer cells and the underlying molecular mechanisms involved, SKOV3 ovarian cancer cells were exposed to the indicated concentrations of metformin (0, 2, 4, 8 and 16 μM). The effects of metformin on SKOV3 cells were monitored using CCK-8 assay for cell viability, colony formation assay for cell growth, scratch assay for cell migration, TUNEL assay and flow cytometry analysis for apoptosis. In the present study, metformin treatment dose-dependently inhibited cell growth with IC 50 values of 16 μM, induced cell apoptosis and decreased the capacity of cell migration. The stemness of SKOV3 cells was impaired, as indicated by significant decrease in stem cell markers SOX2 and OCT4 expressions. Increased capillary-like structure formation and downregulated VEGF and TGFβ1 expressions were observed in response to metformin treatment. Furthermore, western blot showed that 16 μM metformin significantly decreased MPS-1 protein followed by the downregulation of IL-6 protein expression and phosphorylation of Stat3. Collectively, these data indicate that metformin exerts anticancer effects by suppressing stemness and angiogenesis, which at least in part attributes to MPS-1-mediated IL-6/p-Stat3 signaling.