Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo

Li,Xin; Xu,Jinmei; Tang,Xi; Liu,Yilun; Yu,Xiaoping; Wang,Zhi; Liu,Weihua

doi:10.3892/mmr.2016.4990

Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo

Authors:
- Xin Li
- Jinmei Xu
- Xi Tang
- Yilun Liu
- Xiaoping Yu
- Zhi Wang
- Weihua Liu
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Affiliations: Administrative Office, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Scientific Research, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Public Health, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
Published online on: March 16, 2016 https://doi.org/10.3892/mmr.2016.4990
Pages: 4007-4013

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Abstract

Trastuzumab (Herceptin®) is a recombinant humanized monoclonal antibody that is targeted against the human epidermal growth factor receptor 2 (HER2) tyrosine kinase receptor. Trastuzumab has been successfully used to treat patients with HER2-positive breast cancer, which accounts for ~25% of invasive breast cancer. However, the majority of patients who initially respond to trastuzumab demonstrate disease progression within 1 year of treatment. Therefore, identifying alternative drugs that overcome trastuzumab resistance and target HER2 may increase the magnitude and duration of response. Through a high‑throughput screening approach, we previously identified numerous anthocyanins that exert activity in HER2‑positive human breast cancer cell lines. The present study aimed to evaluate the anti‑tumor properties of anthocyanins against parental HER2‑positive cells and derivative trastuzumab‑resistant cells in vitro and in vivo. Cell proliferation, western blotting, Annexin V staining, migration and invasion assays were used to determine the effects of anthocyanins in vitro. Cyanidin-3-glucoside and peonidin-3-glucoside were able to inhibit phosphorylation of HER2, induce apoptosis, suppress migration and invasion, and inhibit tumor cell growth. Coupled with the fact that anthocyanins have been used for decades as supplements for the treatment of various types of cancer in Asia, the present study may have established a framework for the development and testing of anthocyanins as a novel treatment paradigm used to overcome classical trastuzumab-resistance and to improve the outcome of this disease.

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