Metform Ininhibition Induced By Advanced Glycosylation End Products Colorectal Cancer Cell Invasion And Epithelial Mesenchymal Transformation

Objective To explore the effects of Metformin on the proliferation, invasion and epithelial-mesenchymal transition (EMT) of human colorectal cancer (CRC) cells.Methods The SW480 cells were divided into a control group, AGEs group, metformin group and metformin+ AGEs group.Those groups were treated with PBS, advanced glycation end products, metformin, advanced glycation end products+ metformin.MTT was used for detecting metformin on SW480 cell viability.Propidium iodide staining cells DNA content was evaluated the cell cycle. Annexin V-FITC and propidium iodide double staining for apoptosis of the four groups were detected SW-480.Used Boyden chamber invasion assay SW480 cells invasive ability.Western Blotting assay were used for detecting E-cadherin and Vimentin protein levels.Results(1) AGEs group’absorbance value at 24 hours,48 hours and 72 hours were significantly higher than the control group (P<0.05);Metformin group’absorbance value at 12 hours,24 hours,48 hours were no significant higher than the control group (P>0.05);AEGs+ metformin group at 24 hours,48 hours and 72 hours the absorbance values significantly less than the AGEs group (P<0.05).(2) The proportion of G0/G1 phase in AGEs group was significantly lower than the control group,The proportion of S phase in AGEs group was significantly lower than the control group.The proportion of G0/G1 phase in AGEs+metformin group were significantly higher than the AGEs group,The proportion of S phase in AGEs+ metformin group was significantly lower than the AGEs group (P<0.05).There were no significant differences in G2/M phase ratio between the control group, AGEs group, metformin group and AGEs+ metformin group(P>0.05).(3) There was no significant difference in rate of apoptosis between AGEs group and the control group(P>0.05);The apoptosis rate of Metformin group and AGEs+ metformin group were significantly higher than control group (P<0.05);The apoptosis rate of AGEs+ metformin group were significantly higher than the metformin group (P＜0.05).(4) There were no significant differences in cell invasion index between metformin group and the control group (P>0.05);The index of cell in AGEs group invasion was significantly higher than the control (P<0.05);The index of cell in AGEs + metformin group was significantly less than the AGEs group (P<0.05).(5) There were no significant differences in expression level of E-cadherin and Vimentin between the metformin group and the control group (P>0.05);The expression levels of AGEs group was significantly lower than the control group, Vimentin expression levels of E-cadherin in AGEs was significantly higher than the control group (P<0.05);The expression levels of E-cadherin in AGEs+ metformin group was significantly higher than the AGEs group,the expression levels of Vimentin in AGEs+ metformin group was significantly lower than the AGEs group (P＜0.05). Conclusions Our results show that metformin has effects on proliferation, cell cycle, apoptosis, invasion, and EMT of human CRC cells induced by AGEs.