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Article

Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells

  • Authors:
    • Jingbo Zhang
    • Hui Xu
    • Xueyan Zhou
    • Yanyu Li
    • Tong Liu
    • Xiaoxing Yin
    • Bei Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221004, P.R. China, School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China
  • Pages: 4949-4956
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    Published online on: September 4, 2017
       https://doi.org/10.3892/ol.2017.6877
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Abstract

Diabetes mellitus (DM) is an important factor that contributes to the development of type I endometrial cancer (EC). Previous studies have demonstrated that metformin decreases mortality and risk of neoplasms in patients with DM. Since estrogen and estrogen receptor (ER) expression has been associated with the development of EC, the present study aimed to investigate the effects of metformin on cell proliferation and ER expression in EC cell lines that are sensitive to estrogen. The viability and proliferation of Ishikawa and HEC‑1‑A cells were measured following treatment with metformin and/or a 5' AMP‑activated protein kinase (AMPK) inhibitor (compound C) with or without treatment with estradiol (E2). In addition, the levels of ERα, ERβ, AMPK, ribosomal protein S6 kinase β‑1 (p70S6K), myc proto‑oncogene protein (c‑myc) and proto‑oncogene c‑fos (c‑fos) were measured following treatment. Metformin significantly decreased E2‑stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. In addition, metformin significantly inhibited ERα expression while increasing ERβ expression, whereas treatment with compound C reversed these effects. Reverse transcription‑quantitative polymerase chain reaction analysis demonstrated that c‑fos and c‑myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen‑mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Xu H, Zhou X, Li Y, Liu T, Yin X and Zhang B: Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells. Oncol Lett 14: 4949-4956, 2017.
APA
Zhang, J., Xu, H., Zhou, X., Li, Y., Liu, T., Yin, X., & Zhang, B. (2017). Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells. Oncology Letters, 14, 4949-4956. https://doi.org/10.3892/ol.2017.6877
MLA
Zhang, J., Xu, H., Zhou, X., Li, Y., Liu, T., Yin, X., Zhang, B."Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells". Oncology Letters 14.4 (2017): 4949-4956.
Chicago
Zhang, J., Xu, H., Zhou, X., Li, Y., Liu, T., Yin, X., Zhang, B."Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells". Oncology Letters 14, no. 4 (2017): 4949-4956. https://doi.org/10.3892/ol.2017.6877
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Xu H, Zhou X, Li Y, Liu T, Yin X and Zhang B: Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells. Oncol Lett 14: 4949-4956, 2017.
APA
Zhang, J., Xu, H., Zhou, X., Li, Y., Liu, T., Yin, X., & Zhang, B. (2017). Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells. Oncology Letters, 14, 4949-4956. https://doi.org/10.3892/ol.2017.6877
MLA
Zhang, J., Xu, H., Zhou, X., Li, Y., Liu, T., Yin, X., Zhang, B."Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells". Oncology Letters 14.4 (2017): 4949-4956.
Chicago
Zhang, J., Xu, H., Zhou, X., Li, Y., Liu, T., Yin, X., Zhang, B."Role of metformin in inhibiting estrogen‑induced proliferation and regulating ERα and ERβ expression in human endometrial cancer cells". Oncology Letters 14, no. 4 (2017): 4949-4956. https://doi.org/10.3892/ol.2017.6877
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