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The effects of bufadienolides on HER2 overexpressing breast cancer cells

  • Original Article
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Tumor Biology

Abstract

HER2 is a proto-oncogene frequently amplified in human breast cancer, its overexpression is correlated with tamoxifen resistance and decreased recurrence-free survival. Arenobufagin and bufalin are homogeneous bufadienolides of cardiac glycosides agents. In this research, we studied the effects of arenobufagin and bufalin on cellular survival and proliferation of HER2 overexpressing breast cancer cells and the mechanism under the results including the direct effect on HER2 downstream pathways. Our results showed that arenobufagin and bufalin could significantly inhibit the proliferation and survival of HER2 overexpressing breast cancer cells, along with the declination of SRC-1, SRC-3, nuclear transcription factor E2F1, phosphorylated AKT, and ERK. And the combination of each bufadienolide in low dose with tamoxifen could significantly enhance the inhibitory effect of tamoxifen on HER2 overexpressing breast cancer cells. All above suggest that arenobufagin and bufalin may be potential therapy adjuvants for HER2 overexpressing breast cancer therapy.

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Abbreviations

BC:

Breast cancer

MAPK:

Mitogen-activated protein kinase

AKT:

Protein kinase B

SRC-1:

Steroid receptor coactivator-1

SRC-3:

Steroid receptor coactivator-3, TCM, traditional Chinese medicine

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was supported by funds from the Liaoning Province Natural Science Foundation of China (No.2013023043) and National Natural Science Foundation of China (No.510575). The authors who received the funding is Yuhui Yuan. The funders had no role in the study design, data collection and analysis, decision to publish, or the preparation of the manuscript.

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Authors and Affiliations

  1. Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China

    Tianjiao Wang, Haifeng Jin, Peng Zhang, Yueyue Wang, Jinjin Pan & Yuhui Yuan

  2. College of Pharmacy, Dalian Medical University, Dalian, China

    Lin Mu & Xiaochi Ma

  3. Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China

    Jian Miao

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  1. Tianjiao Wang
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Correspondence to Jinjin Pan, Jian Miao or Yuhui Yuan.

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Wang, T., Mu, L., Jin, H. et al. The effects of bufadienolides on HER2 overexpressing breast cancer cells. Tumor Biol. 37, 7155–7163 (2016). https://doi.org/10.1007/s13277-015-4381-3

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