Anti-tumor Effects Of Mfn2in Gastric Cancer

BackgroundGastric cancer is one of the leading causes of cancer-related mortality worldwide. Countries in the Western Pacific Region have the highest reported incidence of gastric cancer; in a recent survey,47%of new gastric cancer cases across the world occurred in China, and more than90%of those cases were found to be advanced. Surgery alone cannot guarantee good long-term survival for patients. Therefore, it is critical that we develop new therapeutic strategies, including molecule-targeted therapy. Mfn2is a potential target gene, and many researchers have confirmed its anti-tumor effect in several malignancy. However, it has not been studied in gastric cancer.ObjectivesExplore the expression difference of mfn2in gastric cancer tissue and normal gastric mucosa tissue, and their relationship with clinicopathological factors. Study the influence of mfn2on various biological features of gastric cancer cell line and explore possible mechanism.MethodsWe studied the expression of mfn2in tissue by IHC, QRT-PCR and western blot. Transfect gastric cancer cells with mfn2-YFP plasmid to make mfn2over-expression. We analyzed the proliferation ability by CCK-8test and colony forming assay, analyzed the cell cycle and cell apoptosis by flow cytometry, and analyzed the invasion and migration ability by transwell assay. We also explored the change of proteins associated with cell cycle, cell apoptosis and invasion ability by western blot.ResultsWe confirmed that mfn2expression was lower in tumor tissue than in normal gastric mucosal tissue, and that it was negatively correlated with tumor size, indicating an anti-tumor role for mfn2. In vitro experiments showed that mfn2over-expression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by down-regulating MMP-2and MMP-9, halted the cell cycle, and induced apoptosis. Western blotting indicated the likely involvement of P21and PI3K/Akt signaling.ConclusionMFN2is a potential anti-tumor gene and potential therapeutic target for treating gastric cancer. The progress of gastric cancer may be delayed by controlling mfn2expression.