β-Elemene, By Restraining Wnt Signaling Pathway, Function As A Dual Role Of Anti-tumor And Anti-inflammation In U251and Macrophage

Background:β-Elemene, as a compound extract in traditional Chinese medicine, known to have promising anti-cancer effects against a broad spectrum of tumors. Whether Wnt signaling pathway and anti-inflammatory effects involved was not well-studied. Recently, there is a close relationship between tumor and inflammation, and relevance between the activity of inducible-nitric oxide and severity of cancer. This thesis, therefore, aim to evaluate whether the Wnt signaling pathway participate in the anti-tumor and anti-inflammatory molecular mechanism underlie the β-Elemene.Methodology/Principal Findings:Determination the β-Elemene optimum concentration by MTT (168.20ug/mL). Dual luciferase reporter gene assay confirmed β-Elemene plays its function in promoting apoptosis by inhibition of the Wnt pathway. Analyze through RT-PCR, real-time PCR, Western blotting and siRNA technologies. The result show β-Elemene can inhibition of iNOs and IL-6transcription by Wnt signaling pathway both in acute inflammation model and in vitro. In lipopolysaccharides (from Escherichia coli) induced-acute inflammation model, the PI3K-AKT signaling pathway activated by Toll-like receptor4(TLR4), which phosphorylate glycogen synthesis kinase3β(GSK-3β)Scrine9. Consequently, inactivate GSK3β and phosphorylate p-catenin Serine552. Thus β-catenin translocate into nucleus, which promote iNOs transcription. In sum, our data shows P-Elemene can suppress the iNOs transcription.Conclusion:β-Elemene restrains cell proliferation and reduces the inflammatory cytokines by inhibition of the Wnt signaling pathway. Thus, The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors, such as β-Elemene,make them an attractive treatment modality towards the control of cancer.