二甲双胍对人胰腺癌细胞迁移的抑制作用

目的:研究二甲双胍对胰腺癌细胞迁移的影响,并初步探讨可能机制.方法:体外培养人胰腺癌细胞株Bxpc-3,予二甲双胍进行干预作为实验组(M组),无药物组作为对照组(C组).MTT检测二甲双胍对Bxpc-3细胞存活率的影响,细胞划痕实验检测划痕愈合率,RT-PCR检测MMP-2、MMP-9 mRNA的表达,Elisa检测细胞培养上清液MMP-2、MMP-9蛋白的分泌量.结果:与对照组相比,MTT结果示二甲双胍可以抑制人胰腺癌细胞株Bxpc-3的增殖,并呈时间-浓度依赖性(F=8.991,124,114.61,P<0.01);划痕实验示二甲双胍干预组12、24、48h与对照组相比划痕愈合率显著下降(t=7.683,9.013,10.471,P<0.01);RT-PCR示二甲双胍干预组MMP-2、MMP-9mRNA的表达显著降低(t=16.563,28.494,P<0.01);Elisa示二甲双胍干预组MMP-2、MMP-9蛋白分泌明显下降(t=9.428,13.542,P<0.01).结论:二甲双胍能显著抑制人胰腺癌细胞株Bxpc-3的增殖及迁移,其主要机制可能与抑制MMP-2、MMP-9活性有关.

Metformin inhibits cell migration in human pancreatic cancer cell line Bxpc-3

AIM: To investigate the effect of metformin on cell migration in human pancreatic cell line Bxpc-3, and to explore the possible mechanism involved. METHODS: Cultured Bxpc-3 cells were treated with metformin as trial group or without metformin as control group. Survival rate of Bxpc-3 cells was determined by methyl thiazolyl tetrazolium (MTT) assay. Scratch assay was used to detect cell migration. Expression of MMP2 and MMP-9 mRNAs was determined by RT-PCR. The contents of MMP-2 and MMP-9 proteins in culture supernatants were determined by ELISA. RESULTS: Compared to control cells, metformin decreased the proliferation of Bxpc-3 cells in a dose-and time-dependent manner (F = 8.991, 124, 114.61, all P < 0.01), reduced the rate of wound closure (t = 7.683, 9.013, 10.471, all P < 0.01), and down-regulated the protein and mRNA expression of MMP-2 and MMP-9 (mRNA: t = 16.563, 28.494, both P < 0.01; protein: t = 9.428, 13.542, both P < 0.01). CONCLUSION: Metformin can inhibit the pro- liferation and migration of Bxpc-3 cells by inhibiting the activity of MMP-2 and MMP-9.