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has been cited by the following article:

• TITLE: Metformin: A possible drug for treatment of endometrial cancer

  AUTHORS: Kosuke Tsuji, Iori Kisu, Kouji Banno, Megumi Yanokura, Arisa Ueki, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Hiroyuki Nomura, Nobuyuki Susumu, Daisuke Aoki

  KEYWORDS: Metformin; Endometrial Cancer; Type 2 Diabetes Mellitus; Mammalian Target of Rapamycin (mTOR); Progesterone Receptor (PR)

  JOURNAL NAME: Open Journal of Obstetrics and Gynecology, Vol.2 No.1, March 31, 2012

  ABSTRACT: Metformin is a widely used first-line drug for treatment of type 2 diabetes mellitus. In recent years, it has been reported that administration of metformin can reduce carcinogenic risk and inhibit proliferation of cancer cells including those from glioma and breast cancer. The underlying mechanism is thought to involve increased LKB-1 phosphorylation induced by metformin, followed by LKB-1 phosphorylation and activation of AMP-activated protein kinase (AMPK), which then inhibits the mammalian target of rapamycin (mTOR) pathway and results in inhibition of cell proliferation. In endometrial cancer, metformin causes cell cycle arrest in vitro, reduces hTERT mRNA, inhibits the mTOR pathway via AMPK, and is involved in inhibition of phosphorylation of S6 ribosomal protein (S6RP). Metformin promotes expression of progesterone receptor by an action opposite to that of insulin-like growth factor-2 (IGF-2) when used in combination with medroxyprogesterone acetate. This enhances the antitumor effect and this approach may be applicable in a clinical setting.