Elevated estrogen receptor β expression in triple negative breast cancer cells is associated with sensitivity to doxorubicin by inhibiting the PI3K/AKT/mTOR signaling pathway.

Content Provider	Europe PMC
Author	Lei, Shanshan Fan, Peizhi Wang, Mengchuan Zhang, Chaojie Jiang, Yu Huang, Shulin Fang, Meng He, Zili Wu, Aiguo
Copyright Year	2020
Abstract	Based on its pathological characteristics, breast cancer is a highly heterogeneous disease. Triple negative breast cancer (TNBC) is an aggressive subtype, and due to a lack of effective therapeutic targets, patients with TNBC do not significantly benefit from endocrine or anti-HER2 therapy. Conventional chemotherapy has been regarded as the only systemic therapy option for TNBC, but its therapeutic efficacy remains limited. Estrogen receptor β (ERβ) has been identified as a tumor suppressor in TNBC. Therefore, the aim of the present study was to identify the role of ERβ in regulating the response to chemotherapy, and to investigate its underlying mechanism in TNBC. MDA-MB-231 and BT549 cells were treated with doxorubicin (DOX), liquiritigenin [Liq, (Chengdu Biopurify Phytochemicals, Ltd.); a specific ERβ agonist], or a combination of DOX and Liq in vitro. The effects of various treatments on cell viability and proliferation were measured using the Cell Counting Kit-8 and colony-formation assays, respectively. MDA-MB-231 and ERβ knockdown (ERβ-KD) MDA-MB-231 cells were selected for the establishment of ERα-/ERβ+ and ERα-/ERβ- cell models, respectively. The two cell models were treated with DOX, Liq or a combination of DOX and Liq. The effects of the treatment on the PI3K/AKT/mTOR signaling pathway were evaluated by assessing the protein expression levels of AKT and mTOR using western blot analysis. Low Liq concentrations increased the sensitivity of MDA-MB-231 and BT549 cells to DOX. Moreover, the synergistic effect of Liq and DOX treatment was associated with the inhibition of the PI3K/AKT/mTOR signaling pathway in MDA-MB-231 cells, and the effect was ERβ-dependent. The results suggested that elevated ERβ expression was associated with sensitivity to doxorubicin by inhibiting the PI3K/AKT/mTOR signaling pathway; therefore, the combined use of conventional chemotherapeutic drugs with ERβ agonists may serve as an effective therapy for TNBC.
ISSN	17920981
Journal	Experimental and Therapeutic Medicine
Volume Number	20
PubMed Central reference number	PMC7388322
Issue Number	2
PubMed reference number	32742395
e-ISSN	17921015
DOI	10.3892/etm.2020.8809
Language	English
Publisher	D.A. Spandidos
Publisher Date	2020-05-28
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Lei et al.
Subject Keyword	estrogen receptor β liquiritigenin triple negative breast cancer PI3K/AKT/mTOR
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Cancer Research