title: Huaier extract synergizes with tamoxifen to induce autophagy and apoptosis in ER-positive breast cancer cells.
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.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Qi
authors.affiliation: Shandong Cancer Hospital and Institute, Jinan, P.R. China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Laboratory Medicine Center, Qilu Hospital of Shandong University, Qingdao, P.R. China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Shangge
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Cun
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Yin
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, P.R. China.|Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045424:Complex Mixtures / Q000737:chemistry*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*; D055454:Trametes; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001688:Biological Products; D045424:Complex Mixtures; D011960:Receptors, Estrogen; C000621679:huaier; D013629:Tamoxifen
keywords: ER-positive breast cancer; Huaier extract; apoptosis; autophagy; tamoxifen