二甲双胍对AGEs诱导人结肠癌细胞SW-480增殖作用的影响及机制的初探  

Effect and mechanism of metformin on AGEs-induced proliferation of colon carcinoma cell line SW-480 induced by AGEs

作　　者：周小智[1,2] 薛耀明[1] 高方[1] 朱波[1] 关美萍[1] 

机构地区：[1]南方医科大学南方医院内分泌代谢科,广州510515 [2]江西省吉安市中心人民医院内分泌科

出　　处：《中国糖尿病杂志》2012年第7期546-548,共3页Chinese Journal of Diabetes

摘　　要：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72h。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、Cy-clinD1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。Objective To explore the effect and mechanism of metforrnin （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 ana!yzed 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 D1 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 D1 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 D1 to suppress the G1/S change and decreasing the telomerase activity.

关 键 词：晚期糖基化终末产物 二甲双胍 SW-480细胞 细胞周期 周期蛋白D1 端粒酶活性 

分 类 号：R735.35[医药卫生—肿瘤]