Effects Of Advanced Glycation End Products On Epithelial-mesenchymal Transition And Cancer Stem Cell Associated Markers In Human Colon Cancer

Object: To investigate the effects of advanced glycation end products(AGEs) on epithelial-mesenchymal transition and cancer stem cell associated markers in human colon cancer cell line SW480 and SW620.Methods: Human colon cancer cell line SW480 and SW620 in the logarithmic phase were randomized in groups, The human colon cancer cell line SW480 and SW620 were treated with AGEs at a dose of 0,50,100,200μg/ml,the migration and invasion ability of the cell were detected by wound healing test and Transwell chamber assay respectively. The percentage of CD133+ cells were tested by flow cytometry. The protein expression levels of RAGE, E-cadherin, Vimentin, Erk1/2,p-Erk1/2 and CD133 were detected by Western blot.Results:1. Wound healing test shows that compared with the control group(0ug/ml),treatment with AGEs(50,100,200μg/ml) enhanced cellular migration.2. Transwell chamber assay shows that compared with the control group(0ug/ml),treatment with AGEs(50,100,200μg/ml) increased the number of Matrigel-permeating cells.3. Flow cytometry test shows that compared with the control group(0ug/ml),treatment with AGEs(50,100,200μg/ml) increased the number of CD133+ cells.4. WB shows that the protein levels of RAGE, Vimentin, p-Erk1/2, CD133 were significantly increased and that of E-cadherin was decreased, while that of Erk1/2 had no change in AGEs treatment groups(50,100,200μg/ml).when compared with control group(0μg/ml).Conclusion: AGEs enhanced cellular migration and invasion, promoted EMT occurs, ultimately increased the proportion of cancer stem cells. The mechanism is that AGEs increase RAGE expression, which stimulates the downstream pathway of Erk1/2 phosphorylation and results in the up regulation of Vimentin and CD133.