Reversal of obesity-driven aggressiveness of endometrial cancer by metformin.
Year: 2019
Type: article
Abstract: BACKGROUND: Obesity and diabetes are associated with increased risk and worse outcomes for endometrial cancer. Metformin is a widely prescribed generic drug for the treatment of type II diabetes and metabolic syndrome and may also have anti-tumorigenic effects. Thus, we assessed the metabolic anti-tumorigenic effects of metformin in (1) human endometrial cancer cell lines under varying glucose concentrations, and (2) a novel genetically engineered mouse model of endometrioid endometrial cancer under obese and lean conditions. METHODS: mouse model of endometrial cancer. Global, untargeted metabolomics was used to identify (1) obesity-associated differences between endometrial tumors and (2) the obesity-dependent effects of metformin in the endometrial tumors. RESULTS: lean-mice, whereas metformin obviously reversed the obesity-driven upregulation of lipid and protein biosynthesis in the obese mice. CONCLUSIONS: lean mice and reversed the detrimental metabolic effects of obesity in the endometrial tumors. Taken together, it is likely that the unique metabolic milieu underlies metformin's improved efficacy in treating endometrial cancer which develop in an obese host environment.
Source: PubMed Central
Authors: Hui Guo, Weimin Kong, Lu Zhang, Jianjun Han, Leslie H Clark, Yajie Yin, Ziwei Fang, Wenchuan Sun, Jiandong Wang, Timothy P Gilliam, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Institutions: University of North Carolina at Chapel Hill, University of Jinan, Shandong Tumor Hospital, Shandong First Medical University, Capital Medical University, Beijing Obstetrics and Gynecology Hospital, University of Tennessee Health Science Center, UNC Lineberger Comprehensive Cancer Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2984093425