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Updated: Oct 24, 2026

In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells
Published on: February 18, 2015
Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation
Genbao Shao1, Wensheng Lai1, Xiaolei Wan2
1School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
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.
Insights
Histone deacetylase inhibitor trichostatin A (TSA) induces ovarian cancer cell differentiation by altering gene expression and cell cycle. Blocking the epidermal growth factor receptor (EGFR) pathway enhances this effect, suggesting a potential new therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ovarian cancer is a leading cause of gynecologic cancer deaths.
- Differentiation therapy for ovarian cancer remains poorly understood.
- Histone deacetylase inhibitors (HDACis) show potential in cancer treatment.
Purpose of the Study:
- To investigate the effect of trichostatin A (TSA) on HO8910 ovarian cancer cell differentiation.
- To elucidate the molecular mechanisms underlying TSA-induced differentiation.
- To explore the role of the epidermal growth factor receptor (EGFR) pathway in this process.
Main Methods:
- Treatment of HO8910 ovarian cancer cells with trichostatin A (TSA).
- Analysis of morphological changes, gene expression (FOXA2, SOX2, OCT4, p21Cip1, cyclin D1), and cell cycle progression.
- Inhibition of the epidermal growth factor receptor (EGFR) signaling pathway.
Main Results:
- TSA induced significant morphological changes indicative of differentiation in HO8910 cells.
- TSA increased differentiation marker FOXA2 and decreased pluripotency markers SOX2 and OCT4.
- TSA suppressed proliferation, caused G1 cell cycle arrest, elevated p21Cip1, and decreased cyclin D1.
- Inhibition of the EGFR pathway potentiated TSA-induced differentiation.
Conclusions:
- Trichostatin A (TSA) effectively induces differentiation in HO8910 ovarian cancer cells.
- TSA impacts key markers of differentiation, pluripotency, and cell cycle regulation.
- Combination therapy with TSA and EGFR inhibitors presents a promising strategy for ovarian cancer differentiation therapy.
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