Long-Term Metformin Effect on Endometrial Cancer Development Depending on Glucose Environment in vitro
Abstract Background: The incidence of endometrial cancer has increased worldwide over the past years. Common risk factors include obesity and metabolic disturbances, like hyperinsulinemia and insulin resistance, as well as prolonged and elevated estrogen exposure. Metformin, an anti-hyperglycemic and insulin-sensitizing biguanide, displayed anti-proliferative effects in recent studies. Therefore, metformin may act as a therapeutic and prophylactic anti-cancer agent in several tissues, including endometrium. Methods: Two different endometrial cancer cell lines, reflecting type I (Ishikawa) and type II endometrial cancer (HEC-1A) were cultured under normoglycemic (5.5mM) or hyperglycemic (17.0mM) conditions and treated with different concentrations of metformin (0.01–5.0mM). Results: Effects of metformin on proliferation, cell viability, clonogenicity and migration were investigated after treatment for 7d. Long-term treatment with metformin showed effects on cellular viability, proliferation and migration of endometrial cancer cells in a concentration- dependent manner in vitro. Additionally, glucose levels affected the outcome of the experiments. Conclusion: Our in vitro findings support the hypothesis that metformin has a direct effect on endometrial tissues and reflects the importance of the local glucose environment, suggesting that metformin may be considered as a potential adjuvant agent in endometrial cancer therapy due to its direct and indirect effects on endometrial development.