Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation

Shao,Genbao; Lai,Wensheng; Wan,Xiaolei; Xue,Jing; Wei,Ye; Jin,Jie; Zhang,Liuping; Lin,Qiong; Shao,Qixiang; Zou,Shengqiang

doi:10.3892/or.2017.5556

Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation

Authors:
- Genbao Shao
- Wensheng Lai
- Xiaolei Wan
- Jing Xue
- Ye Wei
- Jie Jin
- Liuping Zhang
- Qiong Lin
- Qixiang Shao
- Shengqiang Zou
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Affiliations: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Oncology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China, Department of Intensive Care Unit, The Affiliated Third People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212005, P.R. China
Published online on: April 5, 2017 https://doi.org/10.3892/or.2017.5556
Pages: 2891-2896

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Abstract

Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.

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