Objective To explore the effect and mechanism of metformin (Met) on proliferation of colon carcinoma cell line SW-480 induced by advanced glycation end products(AGEs). Methods The SW-480 cells cultured in vitro serving as the subjects for this study and they were divided into four groups: BSA group, AGE group, AGE+Met group, and BSA+Met group. After 72 hours' intervention for each group, the cell viability was assessed by MTT assay, the cell cycle was analyzed by flow cytometry (FCM), the expression of Cyclin D1 was checked by Western blot, and the telomerase activity was examined by tolomeric repeat amplification proctol(TRAP) sliver staining. Results The cell viability, expression of Cyclin Dl and telomerase activity were significantly higher and the G0/G1 was significantly lower in the AGE group than in BSA group(P<0. 05). Compared with the BSA and AGE groups, the cell viability, expression of Cyclin Dl and telomerase activity were significantly lower and the G0/G1 was significantly higher in the AGE+Met and BSA+Met groups(P<0. 05). Conclusion Metformin can decrease the proliferation of SW-480 cells and inhibit the proliferation induced by AGEs through down-regulating the expression of Cyclin Dl to suppress the G1/S change and decreasing the telomerase activity.%目的 探讨二甲双胍(Met)对晚期糖基化终末产物(AGEs)诱导人结肠癌细胞株SW-480增殖作用的影响及机制.方法 实验以体外培养的SW-480细胞为研究对象,分为小牛血清白蛋白(BSA)组,AGE组,AGE+ Met组,BSA+Met组,各组均干预72 h.四氮唑蓝(MTT)法测定细胞活力,流式细胞术测定细胞周期,Western blot检测周期蛋白D1(CyclinD1)的表达水平,TRAP银染法测定端粒酶活性.结果 AGE组的细胞活力、CyclinD1的表达、端粒酶活性较BSA组显著增加,G0/G1期比率较BSA组显著减少(P均＜0.05)；与BSA、AGE组相比,AGE+ Met及BSA+ Met组细胞活力、CyclinD1表达、端粒酶活性显著降低,而G0/G1期比率显著增加(P均＜0.05).结论 二甲双胍能通过下调CyclinD1的表达减慢G1/S期转换,减弱端粒酶活性,抑制SW-480细胞的生长,并抑制AGEs诱导的促SW-480生长作用.
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