Effects of antidiabetic drug metformin on the migration and invasion abilities of human pulmonary adenocarcinoma A549 cell line in vitro.

ABSTRACT

BACKGROUND AND PURPOSE: There is growing evidence that metformin, a clinically widely used drug in the treatment of type II diabetes, may impede the growth of human tumors. However in a recent study it was found that metformin treatment might result in promotion of the angiogenic phenotype and promote early tumorigenic progression. In order to evaluate the relevance between metformin and tumor metastases, we investigated the effects of metformin on the migration and invasion abilities of human pulmonary adenocarcinoma cell line A549 in vitro and explored the possible underlying mechanisms. METHODS: A549 cells were treated with 0.5 mmol/L, 2 mmol/L and 8 mmol/L metformin for 72h. The laterad-migration and invasion abilities of the cells in vitro were evaluated by scratch assay and Boyden-Chamber assay, respectively. Expressions of MMP2 and MMP9 mRNA of the cells before and after metformin treatment were measured by Real-Time PCR. RESULTS: The migration rate of A549 cells was increased after metformin treatment at the concentration of 8mmol/L. The invasion ability was also significantly increased from 37.4±4.6 to 59.8±7.2(P<0.05) by 8mmol/L metformin treatment. No significant difference of the migration and invasion abilities was observed between the Group 0.5mmol/L, 2mmol/L and the Control. The expressions of MMP2 and MMP9 mRNA were both up-regulated after metformin treatment, while in the 8mmol/L Group the genes changes were the most significant. CONCLUSIONS: Metformin can increase the migration speed and enhance invasion abilities of A549 cells in vitro, which may be attributed to the up-regulation of MMP2 and MMP9.