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

Kim,Jinkyoung; Lee,Jiyun; Jang,Soon Young; Kim,Chungyeul; Choi,Yoojin; Kim,Aeree

doi:10.3892/or.2016.4675

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
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Affiliations: Department of Pathology, Korea University Guro Hospital, Guro-gu, Seoul 08308, Republic of Korea, Department of Pathology, College of Medicine, Korea University, Seongbuk-gu, Seoul 02841, Republic of Korea
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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