Oncotarget

Research Papers:

Huaier extract synergizes with tamoxifen to induce autophagy and apoptosis in ER-positive breast cancer cells

Wenwen Qi _, Mingjuan Sun, Xiangnan Kong, Yaming Li, Xiaolong Wang, Shangge Lv, Xia Ding, Sumei Gao, Jinjing Cun, Chang Cai, Xiaoting Wang, Junfei Chen, Aijun Yin and Qifeng Yang

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Oncotarget. 2016; 7:26003-26015. https://doi.org/10.18632/oncotarget.8303

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Abstract

Wenwen Qi1, Mingjuan Sun2, Xiangnan Kong3, Yaming Li1, Xiaolong Wang1, Shangge Lv1, Xia Ding4, Sumei Gao1, Jinjing Cun1, Chang Cai1, Xiaoting Wang1, Junfei Chen1, Aijun Yin5, Qifeng Yang1,6

1Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China

2Shandong Cancer Hospital and Institute, Jinan, P.R. China

3Laboratory Medicine Center, Qilu Hospital of Shandong University, Qingdao, P.R. China

4Department of Oncology, Qilu Hospital, Shandong University, Jinan, P.R. China

5Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China

6Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, P.R. China

Correspondence to:

Qifeng Yang, email: [email protected]

Keywords: Huaier extract, tamoxifen, ER-positive breast cancer, autophagy, apoptosis

Received: December 09, 2015    Accepted: March 02, 2016     Published: March 23, 2016

ABSTRACT

Tamoxifen (TAM) is the most widely used endocrine therapy for estrogen receptor (ER)-positive breast cancer patients, but side effects and the gradual development of insensitivity limit its application. We investigated whether Huaier extract, a traditional Chinese medicine, in combination with TAM would improve treatment efficacy in ER-positive breast cancers. MTT, colony formation, and invasion and migration assays revealed that the combined treatment had stronger anticancer effects than either treatment alone. Huaier extract enhanced TAM-induced autophagy, apoptosis, and G0/G1 cell cycle arrest, as measured by acidic vesicular organelle (AVO) staining, TUNEL, flow cytometry, and western blot. Additionally, combined treatment inhibited tumorigenesis and metastasis by suppressing the AKT/mTOR signaling pathway. Huaier extract also enhanced the inhibitory effects of TAM on tumor growth in vivo in a xenograft mouse model. These results show that Huaier extract synergizes with TAM to induce autophagy and apoptosis in ER-positive breast cancer cells by suppressing the AKT/mTOR pathway.


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