目的：探讨终末糖基化产物（advanced glycation end products，AGEs）对结肠癌SW620细胞上皮间质转化（epithelial-to-mesenchymal transition, EMT）及肿瘤干细胞标志物CD133的影响及其作用机制。方法：用不同浓度（0、50、100、200 μg/ml）的AGEs处理SW620细胞后，采用划痕实验检测细胞的迁移能力；Transwell小室检测细胞的侵袭能力；流式细胞术检测CD133+细胞的含量；Western blotting检测AGEs受体(receptor of AGEs,RAGE)、E-cadherin、Vimentin、ERK1/2、p-ERK1/2、CD133蛋白的表达情况。结果： 与对照组（0 μg/ml）比较,AGEs处理组（50、100、200 μg/ml）在AGEs作用后，SW620细胞24 h迁移距离\[（1.55±0.15）、（158±0.19）、（1.75±0.21）vs （0.95±0.18） mm，均P＜0.05\]及48 h迁移距离\[（211±022）、（2.21±037）、（2.68±023）vs （1.60±0.24） mm，均P＜0.05\]均明显增加；穿过Matrigel胶的数量明显增加\[（176±19.52）、（194±17.70）、（220±25.5）vs （125±26.06） 个，均P<0.05\]；CD133+细胞比例明显增加\[（4.75±149）、（10.34±1.54）、(14.45±2.41）% vs （0.77±0.41），均P<0.05\]。与对照组比较，AGEs处理组（50、100、200 μg/ml）Vimentin、RAGE、p-Erk1/2、CD133蛋白表达明显增加；而ERK1/2蛋白无明显变化；E-cadherin蛋白表达明显减少。结论： AGEs可以提高结肠癌SW620细胞体外的侵袭迁移能力，促进EMT的发生，诱导肿瘤干细胞的生成。其机制可能通过AGE-RAGE受体配体的激活，上调p-ERK1/2,从而调控EMT相关蛋白的表达，促进肿瘤干细胞的生成。

Objective:To investigate the effect of advanced glycation end products(AGEs) on epithelial-mesenchymal transition (EMT) and cancer stem cell associated marker CD133 in human colon cancer cell line SW620 and their mechanism of actions. Methods:After the SW620 cells were treated with AGEs at different concentrations of 0,50,100,200μg/ml, migration and invasion abilities of the SW620 cells were detected by wound healing test and Transwell chamber assay, respectively, percentage of CD133+ cells was tested by flow cytometry, and protein expression levels of receptor of AGEs(RAGE), E-cadherin, Vimentin, ERK1/2, p-ERK1/2 and CD133 were detected by Western blotting. Results: After the treatment of AGEs, compared with the control group (0 μg/ml), cellular migration distances in experiment groups (50, 100, 200 μg/ml) were significantly improved after 24 h (\[1.55±0.15\], \[1.58±0.19\], \[1.75±0.21\] vs \[0.95±0.18\] mm，all P<0.05) and 48 h （\[1.60±0.24\], \[2.11±0.22\], \[2.68±0.23\] vs \[1.60±0.24\] mm, all P<005). In addition, treating the cells with AGEs (50,100, 200 μg/ml) for 48 h remarkably increased number of the cells crossed Matrigel in vitro（ \[176±19.52\], \[194±17.70\], \[220±25.50\] vs \[125±26.06\]，all P＜0.05\] and percentages of CD133+ cell （\[4.75±1.49\], \[10.34±1.54\], \[14.45±2.41\]% vs \[0.77±0.41\]%，all P＜0.05). Expressions of RAGE, Vimentin, p-ERK1/2 and CD133 proteins were significantly increased in the treatment groups comparing with control group; however, the expression of E-cadherin protein was decreased, while that of ERK1/2 protein had not obvious change. Conclusion: AGEs could enhance migration and invasion abilities of the SW620 cells in vitro, promote occurrence of EMT, and induce tumorigenesis of cancer stem cells. Activating ligand of AGE-RAGE, up-regulating p-ERK1/2 prtein and regulating expression of the EMT protein might be a possible mechanism for tumorigenesis of cancer stem cells.

重庆市自然科学基金资助项目（No.cstc2012jjA0038)