Human umbilical cord mesenchymal stem cells inhibit glioma growth

Background: Wnt signaling pathway is a key to occurrence and development of tumor. Several studies have demonstrated that Dickkopf-1 can block intracellular Wnt signalling transmission. Objective: To investigate the inhibitory effect and underlying mechanism of human umbilical cord mesenchymal stem cells on C6 glioma growth by a co-culture system in vitro. Methods: C6 glioma cells were cultured with human umbilical cord mesenchymal stem cells conditioned medium under different concentrations. Cell Counting Kit-8 and flow cytometry analysis were performed to investigate cell proliferation and cell cycle status. Western blotting was used to detect the expression of β-catenin and c-Myc in C6 cells treated with human umbilical cord mesenchymal stem cells conditioned medium. Enzyme-linked immunosorbent assay was adopted to examine the level of Dickkopf-1 secreted by human umbilical cord mesenchymal stem cells. Dickkopf-1 in human umbilical cord mesenchymal stem cells conditioned medium was neutralized by anti-Dickkopf-1 antibody. The effects of antibody neutralization were also determined by the above methods. Results and Conclusion: Human umbilical cord mesenchymal stem cells could inhibit C6 cell expansion and arrest the cell cycle in G0-G1 phase. The expression levels of β-catenin and c-Myc were down-regulated in C6 cells after treatment with human umbilical cord mesenchymal stem cells conditioned medium. The levels of secreted protein Dickkopf-1 were positively correlated with concentrations of human umbilical cord mesenchymal stem cells conditioned medium. The inhibitory effect of human umbilical cord mesenchymal stem cells on C6 cell proliferation was enhanced as the concentration of Dickkopf-1 in human umbilical cord mesenchymal stem cells conditioned medium increased. When Dickkopf-1 was neutralized by anti-Dickkopf-1 antibody, the suppressing effect was attenuated. It demonstrated that human umbilical cord mesenchymal stem cells could inhibit glioma cell growth via secreting the soluble factors, such as Dickkopf-1.