Gao Lian-Bo, Tian Shen, Gao Hong-Hua, Xu Yan-Yuan
Department of Neurology, The 4th Affiliated Hospital of China Medical University, Shenyang, China.
Neuroreport. 2013 Jul 10;24(10):504-8. doi: 10.1097/WNR.0b013e32836277fb.
Fibulin-3 has been considered as a regulator of glioma cell invasion, but little is known about the molecules regulating fibulin-3 expression. Metformin, an oral antidiabetic drug in the biguanide class, is known to inhibit proliferation and metastasis in a variety of cancer cells. In the present study, we determined the effect of metformin on the expression of fibulin-3 in U251 Human glioma cells. Metformin potently suppressed U251 cell adhesion and invasion. Metformin inhibited the expression of fibulin-3 at the transcriptional level. Moreover, metformin abolished the protein expression of fibulin-3 in a concentration-dependent manner. Furthermore, this compound suppressed the expression of matrix metalloproteinase-2, a key effector of glioma cell invasion, regulated by fibulin-3. Taken together, our results suggest that metformin abolishes fibulin-3 expression and subsequently inhibits invasion of glioma cells.
纤维连接蛋白-3被认为是胶质瘤细胞侵袭的调节因子，但对于调节纤维连接蛋白-3表达的分子却知之甚少。二甲双胍是双胍类口服抗糖尿病药物，已知其可抑制多种癌细胞的增殖和转移。在本研究中，我们确定了二甲双胍对U251人胶质瘤细胞中纤维连接蛋白-3表达的影响。二甲双胍有效抑制U251细胞的黏附和侵袭。二甲双胍在转录水平抑制纤维连接蛋白-3的表达。此外，二甲双胍以浓度依赖的方式消除纤维连接蛋白-3的蛋白表达。此外，该化合物抑制基质金属蛋白酶-2的表达，基质金属蛋白酶-2是由纤维连接蛋白-3调节的胶质瘤细胞侵袭的关键效应因子。综上所述，我们的结果表明，二甲双胍消除纤维连接蛋白-3的表达，随后抑制胶质瘤细胞的侵袭。
