Related Experiment Video
Updated: Aug 2, 2026
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Preclinical study of adenoviral p53 gene therapy for esophageal cancer
H Shimada1, T Shimizu, T Ochiai
1Department of Academic Surgery, Chiba University Graduate School of Medicine, Japan.
Abstract:
An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.
Insights
Adenoviral-mediated wild-type p53 gene therapy shows promise for esophageal cancer. This preclinical study demonstrated significant tumor growth suppression in esophageal cancer cell lines and xenografts, suggesting potential clinical application.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Alterations in p53 gene function are critical in esophageal cancer development.
- p53 gene therapy is being explored for other cancers, but its efficacy in esophageal cancer is unproven.
- Esophageal squamous cell carcinoma (ESCC) remains a significant health challenge requiring novel therapeutic strategies.
Purpose of the Study:
- To evaluate the anticancer effects of adenoviral-mediated wild-type p53 gene therapy on human esophageal squamous cell carcinoma.
- To assess the feasibility of Ad5CMV-p53 as a therapeutic agent for esophageal cancer.
- To investigate the molecular mechanisms underlying p53 gene therapy in ESCC.
Main Methods:
- Utilized normal esophageal epithelial cells (EN53F) and two p53-altered human esophageal cancer cell lines (ECGI-10, T.Tn).
- Administered recombinant adenoviral vector Ad5CMV-p53 to assess transduction efficiency, p53 and p21 protein expression, apoptosis induction, and growth suppression.
- Evaluated tumor growth suppression in T.Tn xenografts in nude mice.
Main Results:
- Ad5CMV-p53 transduction efficiency reached 80%-100% at 300 plaque-forming units (PFU)/cell.
- Significant growth suppression was observed in both esophageal cancer cell lines following Ad5CMV-p53 infection.
- Western blot confirmed exogenous p53 expression and p21 induction; TUNEL staining indicated apoptotic cell death.
- T.Tn xenografts showed significant growth suppression upon Ad5CMV-p53 transduction.
Conclusions:
- Adenoviral-mediated wild-type p53 gene therapy (Ad5CMV-p53) effectively suppresses the growth of human esophageal squamous cell carcinoma.
- The therapy induces apoptosis and increases p53 and p21 protein expression in cancer cells.
- Ad5CMV-p53 demonstrates potential as a therapeutic agent for locally advanced esophageal cancer.
More Related Videos
05:45In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
10:42Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion
Published on: July 6, 2022