High Glucose Levels Interferes the Endometrial Cancer Cell Response to Metformin Treatment over Time

Endometrial cancer is one of the most common gynecological malignancies worldwide. Hyperinsulinemia and hyperglycemia seems to play a central role in endometrial carcinogenesis. Furthermore, diseases associate with insulin resistance and high blood glucose levels, as seen in polycystic ovary syndrome, obesity, and type II diabetes mellitus are considered as significant risk factors for the development and progression of type I endometrial cancer. Metformin treatment, an insulinsensitizing agent, has been suggested as therapy to inhibit cellular overgrowth and hyperplasia under these clinical conditions possibly preventing different types of cancer. This study evaluated in an environment with high glucose levels the population doubling behavior of endometrial cancer cells over time under hyperinsulinemic condition as well as therapeutic concentration of metformin in a longterm setting. The endometrial cancer cells not only showed resistance to metformin therapeutic dose but also respond to the treatment increasing drastically the cellular growth and aggressiveness in the presence of high glucose levels