AB49. Anti-tumor effects of Mfn2 in gastric cancer
Geer Zhang, Hailong Jin, Xianke Lin, Chao Chen, Xiaosun Liu, Qing Zhang, Jiren Yu
Background: Gastric 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 than 90% 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. Mfn2 is 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.
Objective: To explore the expression difference of mfn2 in gastric cancer tissue and normal gastric mucosa tissue, and their relationship with clinicopathological factors, and to investigate the influence of mfn2 on various biological features of gastric cancer cell line and its possible mechanism.
Methods: We studied the expression of mfn2 in tissue by IHC, QRT-PCR and western blot. Gastric cancer cells with mfn2-YFP plasmid were transfected to make mfn2 over-expression. The proliferation ability was analyzed by CCK-8 test and colony forming assay; the cell cycle and cell apoptosis were dected by flow cytometry; and the invasion and migration ability was studied by transwell assay. We also explored the change of proteins associated with cell cycle, cell apoptosis and invasion ability by western blot.
Results: It is confirmed that mfn2 expression was lower in tumor tissue than in normal gastric mucosal tissue, and it was negatively correlated with tumor size, indicating an anti-tumor role for mfn2. In vitro experiments showed that mfn2 over-expression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by down-regulating MMP-2 and MMP-9, halted the cell cycle, and induced apoptosis. Western blotting indicated the likely involvement of P21 and PI3K/Akt signaling.
Conclusions: MFN2 is a potential anti-tumor gene and therapeutic target for treating gastric cancer. The progression of gastric cancer may be delayed by controlling mfn2 expression.
Keywords: Gastric cancer; Mfn2; biomarker; anti-tumor gene
