IL-6 Promotes Cell Invasion And Proliferation Via AKT Signaling Pathway In Human Gastric Cancer Cells

Objective Gastric cancer ranks fourth in incidence in the most commom malignancy, and ranks second in mortality in the world.Although the incidence of gastric cancer has declined in some regions in the world in recent years, gastric cancer continnes to present a great challenge due to most cases being diagnosed in advanced stages with poor prognosis.As an important family member of cytokine, IL-6 has been proved to play an essential role in cancer progression. It is reported that marked relationships existed between elevated serum IL-6 levels and tumor stages, with poor prognosis in gastric cancer patients. However, the precise roles of IL-6 in gastric cancer remain undiscovered. We here tried to investigate the effects of IL-6 on gastric cancer cell invasion and proliferation in vitro and then to explore the underlying molecular mechanisms.Methods: MKN-45 cells were disposed by various concentrations of IL-6(0, 20, 50, 100 ng/ml). CCK-8 assay and Transwell assay were performed to assess the effects of IL-6 on gastric cancer cell proliferation and invasion respectively. Protein levels of total-Akt, p-Akt, MMP-9 and c-Myc were detected by western blot analysis. The inhibitor of Akt(SH-5) was used to further confirm whether Akt pathway were involved in IL6-induced enhancement of proliferative and invasive ability in gastric cancer cells, as well as MMP-9 and c-Myc overexpression.Results: The CCK-8 assay and Transwell assay showed the ability of MKN-45 cell proliferation and invasion in group(20, 50, 100 ng/ml) were significantly increased than group(0 ng/ml)(P<0.05). Western blot analysis indicated that IL-6 up-regulated the expression of p-Akt, MMP-9 and c-Myc respectively. Furthermore, the inhibition of of Akt pathway(SH-5) obviously reduced the IL-6-stimulated effects on gastric cancer cell proliferation and invasion with down-regulation of MMP-9 and c-Myc, implying the involvement of Akt pathway in the effects of IL-6 on gastric cancer cells.Conclusions: IL-6 may promote proliferation and invasion in human gastric cancer cells by stimulating c-Myc and MMP-9 expression via Akt pathway.