In order to improve our understanding of the potential preventive and therapeutic role of
metformin, the present study aimed to investigate the capability of low-dose
metformin in the efficient inhibition of
cancer development and the reduction of the
metastasis of endometrial
adenocarcinoma type I and primary endometrial epithelial cells (eEPs), with the drug acting as a treatment in a hyperinsulinemic environment exposed to high and normal
glucose conditions. The Ishikawa endometrial
adenocarcinoma cell line and primary eEPs were exposed to an environment with high (17 mM) or normal
glucose (5 mM) and treated with
insulin, low-dose
metformin (0.1 mM) or a combined treatment. Metastatic potential was assessed by migration and invasion assays, and relative cell proliferation was determined.
Metformin at a low dose potently inhibited the
insulin action, decreasing the ability of the
endometrial cancer (EC) cell line to migrate and invade in a high and normal
glucose environment, and decreasing the migration ability of the primary eEPs. In the EC cell line, the
insulin treatment increased the proliferation, without any subsequent reduction of proliferation by the addition of 0.1 mM
metformin; however, relative cell proliferation sensitivity to
metformin was observed in the range between 1 and 5 mM regardless of the
glucose concentration present. Overall,
metformin at 0.1 mM is not efficient enough to decrease the proliferation in an EC cell line. However, at this concentration,
metformin can inhibit the
insulin action in endometrial epithelial
cancer cells, demonstrating an anti-metastatic effect in high and normal
glucose environments.