Effects Of Iron Overload On Proliferation And Invasion Of Human Gastric Cancer Cells

Objective: To investigate the effects of iron overload on proliferation and invasion in human gastric cancer cell and then to explore the underlying molecular mechanisms, aiming to provide possible strategies for the prevention and therapy of gastric cancer.Method: MKN-45 and SGC-7901 cells were exposed to various concentrations of Ferrous sulfate(0, 50, 100, 200 μM) for 24 h. CCK-8 assay and Transwell assay were performed to assess the effects of iron on gastric cancer cell proliferation and invasion. IL-6 was determined by ELISA and protein levels of MMP-9, c-Myc, total-ERK1/2 and p-ERK1/2 were detected by western blot analysis. The inhibitor of ERK1/2(U0126) was used to elucidate whether ERK1/2 pathway were involved in iron-overload-induced enhancement of proliferative and invasive ability in gastric cancer cells, as well as MMP-9, c-Myc and IL-6 overexpression.Results: The CCK-8 assay showed an increased OD value indicating MKN-45 and SGC-7901 cell proliferative ability in group(50, 100, 200 μM) than group(0 μM)(P<0.05). Transwell assay showed that cell numbers on the lower surface were significantly increased in group(50, 100, 200 μM) than group(0 μM)(P<0.05). Western blot analysis and ELISA indicated that ferrous sulfate up-regulated the expression of MMP-9, c-Myc, p-ERK1/2 and IL-6 respectively. The inhibition of of ERK 1/2 pathway suppressed the iron-overload-induced enhancement of proliferative and invasive ability in gastric cancer cells, as well as reversed MMP-9, c-Myc and IL-6 overexpression.Conclusion: Iron overload may promote the proliferation and invasion in human gastric cancer cells via the activation of ERK1/2- MMP-9/c-Myc/ IL-6.