In vitro model of suicide gene therapy for alpha-fetoprotein-producing gastric cancer

Anticancer Res. 2003 Sep-Oct;23(5A):3795-800.

Abstract

Background: Gastric adenocarcinoma producing alpha-fetoprotein (AFP) has a very poor prognosis. In search of new therapeutic strategies against AFP-producing gastric cancer, we examined the efficacy of suicide gene therapy, which has been effective on AFP-producing hepatoma.

Materials and methods: The herpes simplex virus thymidine kinase (HSVtk) gene was transduced into an AFP-producing gastric adenocarcinoma cell line, FU97, using adenovirus vectors carrying the constructed AFP enhancer/promoter element, followed by ganciclovir (GCV) administration.

Results: Expression of the transgene was evident in FU97 but not in an AFP-nonproducing gastric adenocarcinoma cell line, MKN28, which meant that AFP enhancer/promoter-specific transcriptional targeting was achieved by the vectors. The viability of FU97 but not of MKN28 significantly decreased after the suicide gene therapy in vitro.

Conclusion: Therapeutic application of the AFP enhancer/promoter-specific transfer of the HSVtk gene followed by GCV administration against AFP-producing gastric cancer deserves attention and further research.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / therapy*
  • Adenoviridae / genetics
  • Ganciclovir / therapeutic use
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Humans
  • Promoter Regions, Genetic
  • Simplexvirus / enzymology*
  • Simplexvirus / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / therapy*
  • Thymidine Kinase / biosynthesis
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / metabolism
  • alpha-Fetoproteins / biosynthesis*
  • alpha-Fetoproteins / genetics*

Substances

  • alpha-Fetoproteins
  • Thymidine Kinase
  • Ganciclovir