Suppression of gastric cancer growth by adenovirus-mediated transfer of the PTEN gene

World J Gastroenterol. 2005 Apr 21;11(15):2224-9. doi: 10.3748/wjg.v11.i15.2224.

Abstract

Aim: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells that were wild type for PTEN.

Methods: Adenoviruses expressing PTEN or luciferase as a control were introduced into gastric cancer cells. The effect of exogenous PTEN gene on the growth and apoptosis of gastric cancer cells that are wtPTEN were examined in vitro and in vivo.

Results: Adenovirus-mediated transfer of PTEN (Ad-PTEN) suppressed cell growth and induced apoptosis significantly in gastric cancer cells (MGC-803, SGC-7901) carrying wtPTEN in comparison with that in normal gastric epithelial cells (GES-1) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase and mitogen-activated protein kinase and cell-cycle arrest at the G2/M phase but not at the G1 phase. Furthermore, treatment of human gastric tumor xenografts (MGC-803, SGC-7901) with Ad-PTEN resulted in a significant (P<0.01) suppression of tumor growth.

Conclusion: These results indicate a significant tumor-suppressive effect of Ad-PTEN against human gastric cancer cells. Thus, Ad-PTEN may be used as a potential therapeutic strategy for treatment of gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / secondary
  • Adenocarcinoma, Mucinous / therapy*
  • Adenoviridae / genetics*
  • Animals
  • Cell Division
  • Cell Line, Tumor
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Lymphatic Metastasis
  • Mice
  • Mice, Nude
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • Tumor Suppressor Proteins / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human