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Updated: Jul 18, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
STAT1 activation-induced apoptosis of esophageal squamous cell carcinoma cells in vivo
Junichi Kaganoi1, Go Watanabe, Michio Okabe
1Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Background:
The induction of apoptosis might be a promising treatment for cancers refractory to conventional therapies, such as esophageal cancer. In this study, we examined whether epidermal growth factor-induced growth inhibition results from apoptosis of esophageal squamous cell carcinoma (SCC) cells as a result of STAT1 activation and evaluated whether interferon gamma (IFN-gamma) can induce apoptosis of cancer cells in vivo.
Methods:
To assess the function of STAT1, we established stable transfectants expressing dominant-negative STAT1. Apoptosis was assessed by several experimental techniques, including flow cytometry. Differentiation was evaluated by Western blot test with involucrin used as a marker. In vivo, cancer cells were injected into male BALB/c nu/nu mice. Two weeks later, the mice started to receive injections of IFN-gamma or saline into a tail vein four times per week. Concentrations of IFN-gamma in the tumors were analyzed by enzyme-linked immunosorbent assay. Apoptosis was evaluated by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining.
Results:
Epidermal growth factor inhibited the growth of esophageal SCC cells by causing apoptosis through several pathways involving STAT1 activation. IFN-gamma induced the apoptosis of cancer cells, but it also promoted the differentiation (not apoptosis) of primary cultured cells derived from normal esophageal epithelium. IFN-gamma also inhibited the growth of xenograft tumors of esophageal SCC cells in vivo.
Conclusions:
Our results suggest that IFN-gamma is one candidate for cytokine-based therapy of cancer. IFN-gamma-induced STAT1 activation might be involved in the apoptosis of esophageal SCC cells and in the terminal differentiation of normal squamous cells. Further studies of STAT1 signaling pathways may provide the basis for new targeted therapeutic strategies for esophageal SCC.
Insights
Interferon gamma (IFN-gamma) induces apoptosis in esophageal squamous cell carcinoma (SCC) cells via STAT1 activation, offering a potential cytokine-based cancer therapy. This approach also promotes differentiation in normal esophageal cells.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Apoptosis induction is a promising strategy for treating refractory cancers like esophageal cancer.
- Investigating epidermal growth factor (EGF)-induced growth inhibition and its link to apoptosis in esophageal squamous cell carcinoma (SCC) cells via STAT1 activation.
- Evaluating the in vivo potential of interferon gamma (IFN-gamma) to induce cancer cell apoptosis.
Purpose of the Study:
- To determine if EGF-induced growth inhibition in esophageal SCC cells is mediated by apoptosis through STAT1 activation.
- To assess the efficacy of IFN-gamma in inducing apoptosis of cancer cells in vivo.
- To understand the dual role of IFN-gamma in inducing apoptosis in cancer cells and differentiation in normal cells.
Main Methods:
- Utilized stable transfectants expressing dominant-negative STAT1 to assess STAT1 function.
- Employed flow cytometry and TUNEL staining to evaluate apoptosis.
- Assessed differentiation using Western blot with involucrin as a marker.
- Conducted in vivo experiments using immunodeficient mice bearing esophageal SCC xenografts, treated with IFN-gamma or saline.
Main Results:
- Epidermal growth factor inhibited esophageal SCC cell growth by inducing apoptosis through STAT1 activation.
- Interferon gamma induced apoptosis in cancer cells.
- Interferon gamma promoted differentiation, not apoptosis, in normal esophageal epithelial cells.
- IFN-gamma inhibited the growth of esophageal SCC xenograft tumors in vivo.
Conclusions:
- Interferon gamma is a potential candidate for cytokine-based cancer therapy.
- IFN-gamma-induced STAT1 activation may contribute to apoptosis in esophageal SCC cells and terminal differentiation in normal squamous cells.
- Further research into STAT1 signaling pathways could lead to novel targeted therapeutic strategies for esophageal SCC.
