RRC ID |
77830
|
著者 |
Shimada H, Shimizu T, Ochiai T, Liu TL, Sashiyama H, Nakamura A, Matsubara H, Gunji Y, Kobayashi S, Tagawa M, Sakiyama S, Hiwasa T.
|
タイトル |
Preclinical study of adenoviral p53 gene therapy for esophageal cancer.
|
ジャーナル |
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.
|
巻・号 |
31(7)
|
ページ |
597-604
|
公開日 |
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
|
リソース情報 |
ヒト・動物細胞 |
EC-GI-10(RCB0774) |