Preclinical study of adenoviral p53 gene therapy for esophageal cancer

Citation
H. Shimada et al., Preclinical study of adenoviral p53 gene therapy for esophageal cancer, SURG TODAY, 31(7), 2001, pp. 597-604
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Surgery
Journal title
SURGERY TODAY
ISSN journal
0941-1291 → ACNP
Volume
31
Issue
7
Year of publication
2001
Pages
597 - 604
Database
ISI
SICI code
0941-1291(2001)31:7<597:PSOAPG>2.0.ZU;2-Y
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 clin ical studies in lung cancer and head and neck cancer. However, no preclinic al studies have yet demonstrated an anticancer effect of adenoviral-mediate d wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell car cinoma to test the ability of clinical application. A normal esophageal epi thelial 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 v ector AdSCMV-p53. The transduction efficiency was 60%-80% at 100 plaque-for ming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth sup pression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p5 3 protein expression and p21 protein induction. Apoptotic cell death was ob served with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad 5CMV-p53 demonstrated significant growth suppression. These data suggest th at Ad5CMV-p53 may thus be a potentially effective therapeutic agent for loc ally advanced esophageal cancer.