胰岛素抵抗、肥胖是Ｉ型子宫内膜癌的高危因素，其机制不明，临床工作中胰岛素增敏剂可提供孕激素对子宫不典型增生和早期内膜癌的疗效。我们的前期研究显示二甲双胍可以显著抑制子宫内膜癌细胞的生长，但其作用的分子机制值得深入研究。本课题通过检测胰岛素抵抗相关脂肪因子（脂联素、瘦素、内脂素、抵抗素）对子宫内膜癌细胞雌、孕激素受体、IGFs、糖代谢相关因子、mTOR信号通路之间的影响；二甲双胍对子宫内膜癌细胞脂肪因子及下游信号通路的影响；通过建立胰岛素抵抗的子宫内膜过度增生和子宫内膜癌的动物模型检测胰岛素抵抗对于子宫内膜的影响。探讨胰岛素抵抗相关脂肪因子与子宫内膜过度增殖和子宫内膜癌发病的关系、及二甲双胍对子宫内膜癌细胞抗增殖作用可能机制与环节。以期寻找减少绝经前肥胖妇女子宫内膜异常增生发生的药物；验证二甲双胍治疗子宫内膜癌的安全性和可行性；寻找疗效判断新的靶点，从而使内膜癌患者的预后得到更进一步的改善。

Endometrial cancer is the most common gynecological malignancy, accounting for 6% of all cancers in women. However, a subset of young women in a setting of type 2 diabetes, obesity, polycystic ovarian syndrome is in the high risk of developing endometrial cancer. Their common pathophysiological basis is insulin resistance. But its mechanism is still unknown. A recent case report has shown that combination therapy with metformin and oral contraceptives may reverse progesterone resistant typical endometrial hyperplasia, but this mechanism is unclear. Our preliminary studies have shown that metformin can significantly inhibit the growth of endometrial cancer cells, but its molecular mechanism is worth to explore deeply...This objective of this study is to detect the influence of insulin resistance related adipokines such as adiponectin, leptin, visfatin and resistin on the expression of estrogen and progesterone receptors, insulin growths factor systems and glucose metabolism-related factors and PI3K/AKT, AMPK, mTOR signaling pathway in endometrial cancer cells, which is the downstream signaling pathways in the growth inhibition effects of metformin on endometrial cancer cells and its impact on the insulin resistance related adiopkines. We try to understand the impact of insulin resistance in the endometrial hyperplasia and atyical hyperplasia in the animal models, to investigate insulin resistance in the pathogenesis of endometrial hyperplasia and cancer, and to find out the possible mechanisms and links between metformin and the antiproliferative effect on the endometrial carcinoma cells. ..We aim to confirm metformin or other drugs to reduce the occurrence of endometrial dysplasia in the premenopausal obese women, evaluate the safety and feasibility of metformin in the treatment of endometrial cancer. By looking for the susceptibility of prognosis,a further improvement in the prognosis of patients with endometrial cancer might be achieved.