Adenovirus expressing p27kip1 suppresses growth of established esophageal carcinoma xenografts

World J Gastroenterol. 2005 Nov 14;11(42):6582-6. doi: 10.3748/wjg.v11.i42.6582.

Abstract

Aim: To investigate the growth suppression of adenovirus expressing p27(kip1) on established esophageal tumors in nude mice.

Methods: Esophageal carcinoma xenografts in nude mice were established by tumor tissue mass transplantation. The successfully constructed recombinant adenoviral vectors carrying p27(kip1) gene (Ad-p27(kip1)) were directly injected into the esophageal tumors in nude mice. Compared to control group, the growth curve of tumor was drawn and the growth inhibition rate of tumor was calculated. The histology of tumors was examined by hematoxylin and eosin (H&E) staining. The expression of p27(kip1) and survivin was detected in tumors by immunohistochemical technique.

Results: The growth of tumors in gene therapy group with Ad-p27(kip1) was obviously suppressed compared to control group (0.42+/- 0.08 g vs 1.17+/- 0.30 g, t=6.39, P< 0.01), the inhibition rate of tumor growth reached 64.1%. Pathological detection showed that the tumors in nude mice were poorly differentiated esophageal squamous carcinoma. In addition, the expression of p27(kip1) was increased, while the expression of survivin was decreased in tumors after being transfected with Ad-p27(kip1).

Conclusion: p27(kip1) gene therapy mediated by adenovirus vector has a significant inhibitory effect on esophageal carcinoma in vivo. Up-regulated p27(kip1) expression and down-regulated survivin expression may be its important mechanisms.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Immunohistochemistry
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / metabolism
  • Neoplasm Transplantation
  • Repressor Proteins
  • Survivin
  • Transplantation, Heterologous*

Substances

  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Repressor Proteins
  • Survivin
  • Cyclin-Dependent Kinase Inhibitor p27