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