title: Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis.
abstract: BACKGROUND
  Effective therapies for early endometrial cancer usually involve surgical excision and consequent infertility Therefore, new treatment approaches that preserve fertility should be developed. Metformin, a well-tolerated anti-diabetic drug, can inhibit cancer cell growth. However, the mechanism of metformin action is not well understood. Here we investigate the roles of autophagy and apoptosis in the anti-cancer effects of metformin on endometrial cancer cells.
  
  
  METHODS
  Ishikawa endometrial cancer cells were treated with metformin. WST-8 assays, colony formation assays, flow cytometry, caspase luminescence measurement, immunofluorescence, and western blots were used to assess the effects of metformin on cell viability, proliferation, cell cycle progression, apoptosis, and autophagy.
  
  
  RESULTS
  Metformin-treated cells exhibited significantly lower viability and proliferation and significantly more cell cycle arrest in G1 and G2/M than control cells. These cells also exhibited significantly more apoptosis via both intrinsic and extrinsic pathways. In addition, metformin treatment induced autophagy. Inhibition of autophagy, either by Beclin1 knockdown or by 3-methyladenine-mediated inhibition of caspase-3/7, suppressed the anti-proliferative effects of metformin on endometrial cancer cells. These findings indicate that the anti-proliferative effects and apoptosis caused by metformin are partially or completely dependent on autophagy.
  
  
  CONCLUSIONS
  We showed that metformin suppresses endometrial cancer cell growth via cell cycle arrest and concomitant autophagy and apoptosis.
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Akimasa
authors: A
authors: Takahashi
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Fuminori
authors: F
authors: Kimura
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Akiyoshi
authors: A
authors: Yamanaka
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Akie
authors: A
authors: Takebayashi
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Nobuyuki
authors: N
authors: Kita
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Kentaro
authors: K
authors: Takahashi
authors: Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta-Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Takashi
authors: T
authors: Murakami
keywords: Apoptosis; Autophagy; Endometrial cancer; Metformin