Open Access

Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines

  • Authors:
    • Jinkyoung Kim
    • Jiyun Lee
    • Soon Young Jang
    • Chungyeul Kim
    • Yoojin Choi
    • Aeree Kim
  • View Affiliations

  • Published online on: March 11, 2016     https://doi.org/10.3892/or.2016.4675
  • Pages: 2553-2560
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acquisition of tamoxifen resistance (TR) during anti-estrogenic therapy using tamoxifen is a major obstacle in the treatment of estrogen receptor (ER)-positive breast cancer. As a biguanide derivative, metformin is commonly used to treat type II diabetes. It has recently emerged as a potential anticancer agent. The objective of the present study was to investigate the anticancer activity of metformin in relation to ERα expression and its signaling pathway in ERα-positive MCF-7 and MDA-MB-361 breast cancer cells as well as TR MCF-7 breast cancer cells. Metformin inhibited both protein and mRNA levels of ERα in the presence or absence of estrogen (E2) in the MCF-7, TR MCF-7 and MDA-MB-361 cells. Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERα-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells. Collectively, our results suggest that one of the anticancer mechanisms of metformin could be attributable to the repression of expression and transcriptional activity of ERα. Metformin may be a good therapeutic agent for treating ERα-positive breast cancer by inhibiting the expression and function of ERα. In addition, metformin may be useful to treat tamoxifen-resistant breast cancer.
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May-2016
Volume 35 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Kim J, Lee J, Jang SY, Kim C, Choi Y and Kim A: Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines. Oncol Rep 35: 2553-2560, 2016.
APA
Kim, J., Lee, J., Jang, S.Y., Kim, C., Choi, Y., & Kim, A. (2016). Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines. Oncology Reports, 35, 2553-2560. https://doi.org/10.3892/or.2016.4675
MLA
Kim, J., Lee, J., Jang, S. Y., Kim, C., Choi, Y., Kim, A."Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines". Oncology Reports 35.5 (2016): 2553-2560.
Chicago
Kim, J., Lee, J., Jang, S. Y., Kim, C., Choi, Y., Kim, A."Anticancer effect of metformin on estrogen receptor-positive and tamoxifen-resistant breast cancer cell lines". Oncology Reports 35, no. 5 (2016): 2553-2560. https://doi.org/10.3892/or.2016.4675