Estrogen receptor antagonist fulvestrant inhibits proliferation and promotes apoptosis of prolactinoma cells by regulating the IRE1/XBP1 signaling pathway

Wang,Chao; Bai,Minghan; Wang,Xin; Tan,Chunlei; Zhang,Dongzhi; Chang,Liang; Li,Guofu; Xie,Lingyu; Su,Jun; Wen,Yuan

doi:10.3892/mmr.2018.9379

Estrogen receptor antagonist fulvestrant inhibits proliferation and promotes apoptosis of prolactinoma cells by regulating the IRE1/XBP1 signaling pathway

Authors:
- Chao Wang
- Minghan Bai
- Xin Wang
- Chunlei Tan
- Dongzhi Zhang
- Liang Chang
- Guofu Li
- Lingyu Xie
- Jun Su
- Yuan Wen
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Affiliations: Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China, Department of Hepatobiliary Surgery, The Fourth Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: August 10, 2018 https://doi.org/10.3892/mmr.2018.9379
Pages: 4037-4041

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Abstract

The aim of the present study was to evaluate the effects of an estrogen receptor antagonist, fulvestrant, on proliferation and apoptosis of prolactinoma cells, and to reveal potential regulatory mechanisms. Prolactinoma GH3 cells were treated with 10‑6 mol/l fulvestrant for 2, 4, 8, 12 and 24 h. GH3 cell growth was observed under a microscope and cell viability was detected by MTT assay. Morphological changes of the nuclei in GH3 cells were observed by Hoechst 33258 staining and apoptotic rates were detected by flow cytometry. Preprolactin (PPL) and prolactin (PRL) secretion levels from GH3 cells were measured using ELISA. In addition, the protein expression levels of inositol‑requiring enzyme 1 (IRE1), X‑box binding protein (XBP)‑1 and glucose‑regulated protein, 78 kDa (GRP78) in GH3 cells were detected by western blot analysis. Cell density and cell viability of GH3 cells were significantly reduced in a time‑dependent manner following treatment with fulvestrant (P<0.05). GH3 cells treated with fulvestrant also acquired an apoptotic morphology and the apoptotic rate of GH3 cells was significantly increased by fulvestrant in a time‑dependent manner (P<0.05). PPL and PRL secretion levels were significantly reduced by fulvestrant treatment in a time‑dependent manner (P<0.05). The protein expression levels of IRE1, XBP1 and GRP78 were also significantly reduced in a time‑dependent manner following treatment with fulvestrant (P<0.05). Therefore, fulvestrant may inhibit proliferation and promote apoptosis of GH3 cells by downregulating the IRE1/XBP1 signaling pathway.

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