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Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Metformin is the most prescribed anti-diabetic medication worldwide because of its proven efficacy and limited side effects. In this study, the significant anticancer effect of metformin was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells.

Methods

We tested the growth inhibition assay using MTT cell proliferation, cell cycle assay, apoptosis assessment with flow cytometry using propidium iodide and Annexin V, and autophagy protein expression with western blot analysis.

Results

Metformin inhibited the growth of cancer cells with different concentrations in a dose- and time-dependent manner. Moreover, the inhibition properties observed as a function of increased concentrations of metformin were markedly augmented when the medication was administered in the progesterone-resistant Ishikawa cells, even with a dose as low as 10 mM. The early and late phases of apoptosis were enhanced in the metformin-treated tumour cells that were analyzed. For the Ishikawa cells, the expression of p-AMPK, LC-3, and beclin1 was upregulated after treatment, whereas the AMPK levels were not modulated. Furthermore, for the Ishikawa-PR cells, the protein levels were similarly upregulated. Finally, we observed that the three proteins showed much more variability in Ishikawa-PR cells than in Ishikawa cells.

Conclusion

The application of metformin to target autophagy in endometrial cancer cells provides a new potential treatment for progesterone-resistant endometrial carcinoma.

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Authors and Affiliations

  1. Southern Medical University, 510000, Guangzhou, People’s Republic of China

    Aiming Wang

  2. Navy General Hospital of Chinese PLA, 100000, Beijing, People’s Republic of China

    Aiming Wang

  3. Ningbo No. 2 Hospital, 315010, Ningbo, People’s Republic of China

    Zhihong Zhuo & Huimin Yu

Authors
  1. Zhihong Zhuo
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  2. Aiming Wang
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  3. Huimin Yu
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Corresponding author

Correspondence to Aiming Wang.

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This article does not contain any studies with human participants performed by any of the authors.

Funding

This study was funded by Ningbo natural foundation (Grant Numbers: 2014A610234; 2015A610226).

Conflict of interest

The authors declare that they have no conflict of interest.

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Zhuo, Z., Wang, A. & Yu, H. Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma. Arch Gynecol Obstet 294, 1055–1061 (2016). https://doi.org/10.1007/s00404-016-4148-0

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  • DOI: https://doi.org/10.1007/s00404-016-4148-0

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