Downregulation of XBP1 decreases serous ovarian cancer cell viability and enhances sensitivity to oxidative stress by increasing intracellular ROS levels

Zhang,Gui  Hong; Kai,Jin  Yan; Chen,Miao  Miao; Ma,Qian; Zhong,Ai  Ling; Xie,Su  Hong; Zheng,Hui; Wang,Yan  Chun; Tong,Ying; Tian,Yuan; Lu,Ren  Quan; Guo,Lin

doi:10.3892/ol.2019.10772

Downregulation of XBP1 decreases serous ovarian cancer cell viability and enhances sensitivity to oxidative stress by increasing intracellular ROS levels

Authors:
- Gui Hong Zhang
- Jin Yan Kai
- Miao Miao Chen
- Qian Ma
- Ai Ling Zhong
- Su Hong Xie
- Hui Zheng
- Yan Chun Wang
- Ying Tong
- Yuan Tian
- Ren Quan Lu
- Lin Guo
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Affiliations: Department of Clinical Laboratory, Fudan University, Shanghai Cancer Center, Shanghai 200032, P.R. China
Published online on: August 22, 2019 https://doi.org/10.3892/ol.2019.10772
Pages: 4194-4202
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interaction between endoplasmic reticulum (ER) stress and oxidative stress contributes to the occurrence and development of various types of cancer. The X‑box‑binding protein 1 (XBP1), which is an important transcription factor in ER stress‑related pathways, has also been reported to serve a protective role against oxidative stress. However, the role of XBP1 in serous ovarian cancer (SOC) remains elusive. The aim of the present study was to explore the biological function of XBP1 in SOC cells under normal or oxidative stress conditions. The expression of XBP1 was downregulated in the SOC cell lines A2780 and HO8910 by lentivirus‑mediated short hairpin RNA (shRNA). Cell proliferative ability was evaluated by cell colony formation and viability assays. The sensitivity of ovarian cancer cells to oxidative stress was evaluated using cell survival rate and apoptotic rate, determined by the Cell Counting Kit‑8 assay and flow cytometry, respectively. Reactive oxygen species (ROS) levels were measured by flow cytometry and cell immunofluorescence using a dichlorodihydrofluorescein diacetate probe. The mRNA and protein expression levels were detected by fluorescence quantitative polymerase chain reaction and western blot analysis, respectively. The results demonstrated that XBP1 was overexpressed in SOC compared with normal ovarian epithelial cells, and that downregulation of XBP1 significantly reduced cell proliferative ability. In addition, the downregulation of XBP1 significantly enhanced the sensitivity of SOC cells to H2O2 by increasing the intracellular ROS levels. The phosphorylation level of the mitogen‑activated protein kinase (MAPK) p38 decreased in the cells of the XBP1‑knockdown group. These results indicated that XBP1 may serve a protective role against oxidative stress in SOC cells, and the underlying molecular mechanism may be associated with the downregulation of phosphorylated p38. Therefore, targeting XBP1 may act synergistically with ROS inducers in the treatment of SOC.

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