title: Direct effects of metformin in the endometrium: a hypothetical mechanism for the treatment of women with PCOS and endometrial carcinoma.
abstract: Although a number of in vitro studies have demonstrated the antiproliferative, anti-invasive, and antimetastatic effects of metformin in multiple cancer cell types, its cellular and molecular mechanisms of anti-cancer action in the endometrium of women with polycystic ovary syndrome (PCOS) have not yet been fully elucidated. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are known to be involved in metformin uptake and excretion in cells. In this article, we discuss the novel therapeutic possibilities for early-stage endometrial carcinoma (EC) in women with PCOS focusing on metformin, which might have a direct effect in the endometrium through the OCTs and MATEs. We then review the molecular mechanism(s) of the action of metformin in the endometrium and highlight possible mechanistic insights into the inhibition of cell proliferation and tumor growth and, ultimately, the reversal of early-stage EC into normal endometria in women with PCOS.
authors.affiliation: Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg 40530, Sweden. ruijin.shao@fysiologi.gu.se.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Shao
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Lin
authors.forename: Håkan
authors.initials: H
authors.lastname: Billig
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy*; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D019899:Paracrine Communication; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D027701:Organic Cation Transport Proteins; D008687:Metformin