Metformin inhibits the migration and invasion of esophageal squamous cell carcinoma cells by downregulating the protein kinase B signaling pathway.

Previous studies have suggested that metformin, a biguanide family member widely used as an oral antidiabetic drug, may inhibit proliferation and induce apoptosis in certain types of cancer cell. However, the molecular mechanisms underlying metformin-associated anticancer effects, and in particular antimetastatic effects, remain to be fully understood. The present study assessed the efficacy of metformin in inhibiting the migration and invasion of the esophageal carcinoma cell line EC109, and evaluated the effect of metformin on the protein kinase B (AKT) signaling pathway. EC109 cells were treated with 0, 5, 10 or 20 mM metformin during the logarithmic growth phase. A Transwell assay and western blot analysis revealed that metformin inhibited the migration and invasion of EC109 cells, nuclear factor-κB activation, matrix metallopeptidase 9 and N-cadherin expression in a phosphorylated-AKT dependent manner. These results suggested that metformin inhibits the migration and invasion of human esophageal carcinoma cells by suppressing AKT phosphorylation and regulating the expression of migration- and invasion-associated genes.

Reactive oxygen species and mitochondrial membrane potential are modulated during CDDP-induced apoptosis in EC-109 cells.

cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Deltapsim), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Deltapsim; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Deltapsim are events involved in the apoptotic pathway of EC-109 induced by CDDP.