Metformin inhibits estrogen‐dependent endometrial cancer cell growth by activating the AMPK–FOXO1 signal pathway

• DOI: 10.1111/cas.13083
• Publication Date: 2016-09-16T14:12:52Z
• Authors: Jingfang Zou; Liangli Hong; Chaohuan Luo; Zhi Li; Yuzhang Zhu; Tianliang Huang; Yongneng Zhang; Huier Yuan; Yaqiu Hu; Tengfei Wen; Wanling Zhuang; Bozhi Cai; Xin Zhang; Jiexiong Huang; Jidong Cheng
• Keywords: Biguanide; AMP-Activated Protein Kinase

Metformin is an oral biguanide commonly used for treating type II diabetes and has recently been reported to possess antiproliferative properties that can be exploited the prevention treatment of a variety cancers. The mechanisms underlying this effect have not fully elucidated. Our study shows marked loss AMP ‐activated protein kinase ( AMPK ) phosphorylation nuclear human Forkhead box O1 FOXO 1) in estrogen‐dependent endometrial cancer EC tumors compared normal control endometrium. suppressed cell growth time‐dependent manner vitro ; was cancelled by cotreatment with inhibitor, compound C. decreased 1 increased localization Ishikawa HEC ‐1B cells, non‐significant increase mRNA expression. Moreover, C blocked metformin‐induced changes its protein, suggesting metformin upregulated activity activation. Similar results were obtained after insulin. In addition, transfection si RNA metformin‐inhibited growth, indicating mediated inhibit proliferation. A xenograft mouse model further revealed tumor accompanied downregulated ki‐67 protein. Taken together, these data provide novel mechanism antineoplastic through regulation 1, suggest – pathway may therapeutic target development new drugs.