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Metformin Exhibits an Attractive Antineoplastic Effect on Human Endometrial Cancer by Regulating the Hippo Signaling

Meng Wang1, Qiulin Zhang1,2, Yuehan Li1

  • 1Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Journal of Oncology
|October 13, 2022
PubMed

Insights

Metformin inhibits endometrial cancer cell growth, migration, and invasion by downregulating YAP1. This suggests metformin as a potential chemotherapy alternative with reduced toxicity, particularly for women desiring fertility preservation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Metformin, a common antidiabetic drug, exhibits anticancer properties.
  • Its mechanism in endometrial cancer, especially concerning reproductive toxicity, remains unclear.

Purpose of the Study:

  • To investigate metformin's mechanism of action in human endometrial cancer.
  • To evaluate its potential as a less toxic chemotherapy alternative.
  • To explore the role of YAP1 in metformin's effects.

Main Methods:

  • Treatment of Ishikawa and RL95-2 endometrial cancer cell lines with metformin.
  • Analysis of cell proliferation, migration, invasion, cell cycle, and apoptosis.
  • Gene and protein expression analysis (RT-qPCR, Western blotting).
  • Establishment of YAP1 knockout cells to confirm the mechanism.

Main Results:

  • Metformin inhibited cell growth, migration, and invasion in a dose- and time-dependent manner.
  • Metformin induced G1/G2 cell cycle arrest and increased apoptosis.
  • Metformin significantly reduced YAP1 mRNA and protein expression.
  • YAP1 knockout cells mimicked metformin's effects on cellular behavior.

Conclusions:

  • Metformin demonstrates significant antineoplastic effects in endometrial cancer cells.
  • The Hippo pathway effector YAP1 is a key mediator of metformin's action.
  • Metformin represents a promising, less toxic alternative to conventional chemotherapy for endometrial cancer, especially for fertility-sparing treatments.

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