RRC ID 77830
Author Shimada H, Shimizu T, Ochiai T, Liu TL, Sashiyama H, Nakamura A, Matsubara H, Gunji Y, Kobayashi S, Tagawa M, Sakiyama S, Hiwasa T.
Title Preclinical study of adenoviral p53 gene therapy for esophageal cancer.
Journal Surg Today
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.
Volume 31(7)
Pages 597-604
Published 2001-1-1
DOI 10.1007/s005950170093
PII 10.1007/s005950170093
PMID 11495154
MeSH Adenoviruses, Human / genetics* Animals Apoptosis Cell Survival Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 Cyclins / metabolism Esophageal Neoplasms / pathology Esophageal Neoplasms / therapy* Esophagus / cytology Genes, p53* Genetic Therapy / methods* Genetic Vectors Humans In Vitro Techniques Mice Mice, Nude Recombination, Genetic Transduction, Genetic Tumor Cells, Cultured
IF 1.878
Human and Animal Cells EC-GI-10(RCB0774)