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Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through oestrogen receptor α (ERα) re-expression

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Abstract

Endocrine therapy is an important therapeutic approach for the treatment of oestrogen receptor (ER)-positive breast cancer. However, a number of these endocrine therapies can fail when the tumour loses its ER expression during treatment. To date, few studies have explored the potential clinical significance of traditional Chinese medicine in inducing the reversal of resistance to endocrine therapy in breast cancers. We used the ERα-negative MCF7 breast cancer cell line to create a tamoxifen (TAM)-resistant cell line, MCF7/TAM cells. After treating MCF7/TAM cells with ELE to induce the re-expression of ERα, we investigated the role and molecular mechanisms by which elemene (ELE) promotes the reversal of resistance to endocrine therapy. We discovered that treatment with 10 μg/ml ELE restored the sensitivity of MCF7/TAM cells to TAM. RT-PCR analysis revealed that ELE treatment upregulated ERα mRNA levels in MCF7/TAM cells, and immunohistochemistry confirmed the upregulation of ERα expression. Western blot analysis revealed that ELE treatment decreased the protein expression levels of Ras, MEK1/2 and p-ERK1/2 in MCF7/TAM cells. The loss of ERα expression was the primary reason for TAM resistance in MCF7 cells. The ELE-induced reversal of TAM resistance was mediated by the upregulation of ERα mRNA and the re-expression of ERα through the MAPK pathway.

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Acknowledgments

We would like to thank Chaohui Wang, Ling Li and Yan Wang from the Central Laboratory of the Second Affiliated Hospital of Dalian Medical University for providing technical consultation for this study.

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Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021, China

    Bin Zhang

  2. Department of Oncology, Shandong Cancer Hospital and Institute, Jinan, 250117, China

    Xia Zhang

  3. Department of General Surgery, The Affiliated Hospital of Guilin Medical Collage, Guilin, 978636, China

    Bo Tang

  4. Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, China

    Peishi Zheng & Yang Zhang

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  1. Bin Zhang
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  2. Xia Zhang
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  3. Bo Tang
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  5. Yang Zhang
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Correspondence to Yang Zhang.

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Zhang Bin and Zhang Xia contributed equally to this article.

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Zhang, B., Zhang, X., Tang, B. et al. Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through oestrogen receptor α (ERα) re-expression. Breast Cancer Res Treat 136, 399–406 (2012). https://doi.org/10.1007/s10549-012-2263-6

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  • DOI: https://doi.org/10.1007/s10549-012-2263-6

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