Estrogen receptor β suppresses inflammation and the progression of prostate cancer

Xiao,Long; Luo,Yaohui; Tai,Rongfen; Zhang,Ningnan

doi:10.3892/mmr.2019.10014

Estrogen receptor β suppresses inflammation and the progression of prostate cancer

Authors:
- Long Xiao
- Yaohui Luo
- Rongfen Tai
- Ningnan Zhang
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Affiliations: Department of Urology, The First People's Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, Yunnan 650041, P.R. China
Published online on: March 6, 2019 https://doi.org/10.3892/mmr.2019.10014
Pages: 3555-3563
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies demonstrated that estrogen receptor β (ERβ) signaling alleviates systemic inflammation in animal models, and suggested that ERβ‑selective agonists may deactivate microglia and suppress T cell activity via downregulation of nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB). In the present study, the role of ERβ in lipopolysaccharide (LPS)‑induced inflammation and association with NF‑κB activity were investigated in PC‑3 and DU145 prostate cancer cell lines. Cells were treated with LPS to induce inflammation, and ELISA was performed to determine the expression levels of inflammatory cytokines, including tumor necrosis factor‑α (TNF‑α), monocyte chemoattractant protein 1 (MCP‑1), interleukin (IL)‑1β and IL‑6. MTT and Transwell assays, and Annexin V/propidium iodide staining were conducted to measure cell viability, apoptosis and migration, respectively. Protein expression was determined via western blot analysis. LPS‑induced inflammation resulted in elevated expression levels of TNF‑α, IL‑1β, MCP‑1 and IL‑6 compared with controls. ERβ overexpression significantly inhibited the LPS‑induced production of TNF‑α, IL‑1β, MCP‑1 and IL‑6. In addition, the results indicated that ERβ suppressed viability and migration, and induced apoptosis in prostate cancer cells, which was further demonstrated by altered expression of proliferating cell nuclear antigen, B‑cell lymphoma 2‑associated X protein, caspase‑3, E‑cadherin and matrix metalloproteinase‑2. These effects were reversed by treatment with the ERβ antagonist PHTPP or ERβ‑specific short interfering RNA. ERβ overexpression reduced the expression levels of p65 and phosphorylated NF‑κB inhibitor α (IκBα), but not total IκBα expression in LPS‑treated cells. In conclusion, ERβ suppressed the viability and migration of the PC‑3 and DU145 prostate cancer cell lines and induced apoptosis. Furthermore, it reduced inflammation and suppressed the activation of the NF‑κB pathway, suggesting that ERβ may serve roles as an anti‑inflammatory and anticancer agent in prostate cancer.

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