| 【Background】:Gastric cancer is the third most common cause of cancer deaths worldwide.Invasion and metastasis after gastric cancer treatment is still an important obstacle to the treatment effect.5-lipoxygenase can enhance cell proliferation,migration and invasion.And epithelial-mesenchymal transition(EMT)is considered an important process of tumor metastasis and invasion.However,the role and mechanism of 5-LOX on proliferation,migration and invasion of gastric cancer have not been systematically elucidated 【Objective】:To explore the role and mechanism of EphA2 in EMT in gastric cancer 【Methods】:Clinical specimens of gastric cancer were collected and the expression of 5-LOX in gastric cancer tissues and its relationship with clinicopathological features were analyzed by immunohistochemistry.Kaplan-Meier survival curves and log-rank test were used to evaluate the effect of 5-LOX on the prognosis of gastric cancer.Transwell migration and invasion assay were used to detect the effect of 5-LOX on the migration and invasion of gastric cancer cells.Western blot was used to explore whether overexpression of 5-LOX coμld promote the expression of EMT-related proteins in gastric cancer cells.The subcutaneous and celiac tumors in nude mice were established to investigate the effect of 5-LOX on the proliferation and metastasis of gastric cancer cells in vivo.The potential mechanism of 5-LOX-mediated EMT in gastric cancer cells was investigated using the MAPK/ERK pathway inhibitor U0126.【Resμlts】: 1.Immunohistochemistry experiments showed that the expression of 5-LOX in gastric cancer tissues was significantly increased,and it was significantly associated with some clinicopathological features.2.The Kaplan-Meier survival curve showed that 5-LOX can significantly reduce the postoperative survival time of gastric cancer patients.3.CCK-8 cell proliferation assay showed that the OD value of 5-LOX-overexpressing gastric cancer cells was significantly higher than that of the control group.The OD value of 5-LOX-silenced gastric cancer cells was significantly lower than that of the control group;transwell migration and invasion experiments showed that the number of gastric cancer cell through the migration and invasion transwell chamber in 5-LOX-overexpressing group was significantly higher than that of the control group,and the number of gastric cancer cells that silenced 5-LOX through the migration and invasion transwell chamber was significantly lower than that of the control group.4.Western blot and immunofluorescence experiments showed that compared with the control group,the expression of E-cadherin was significantly decreased in the 5-LOXoverexpressing gastric cancer cells and the expression of N-cadherin and p-ERK was significantly increased.However,compared with the control group,the expression of E-cadherin was significantly increased in the 5-LOX-silenced gastric cancer cells,and the expression of N-cadherin and p-ERK was significantly decreased.5.Subcutaneous and abdominal tumorigenesis experiments in nude mice showed that the volume and weight of subcutaneous tumors in the 5-LOX group were significantly greater than those in the control group.Metastatic tumors at the base of the liver,in the abdominal cavity and the mesenterium in the 5-LOX group were significantly more than those in the control group.Ascites in the 5-LOX group were more severe than the control group.6.Western blot showed that compared with 5-LOX-overexpressing gastric cancer cells,the expression of E-cadherin was up-regμlated and the expression of N-cadherin was down-regμlated in gastric cancer cells treated with U0126.【Conclusions】: 1.5-LOX was significantly increased in gastric cancer and associated with poor prognoses in gastric cancer patients.2.5-LOX mediates the EMT in gastric cancer cells.3.5-LOX promotes EMT in gastric cancer cells by activating the MAPK/ERK pathway. |
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