[Experimental study on human pancreatic carcinoma treated by cytosine deaminase gene therapy]

Zhonghua Yi Xue Za Zhi. 2000 Apr;80(4):249-51.
[Article in Chinese]

Abstract

Objective: To explore the possibility of Escherichia coli cytosine deaminase (CD) gene on human pancreatic carcinoma gene therapy.

Methods: Recombinant adenoviruses containing a carcinoembryonic antigen (CEA) promoter were transiently introduced into SW1990, Capan-2 and Hela cells, separately. The expression of CD gene mRNA was examined by RT-PCR. CD protein level in the transduced cells was analyzed by Western blotting. The sensitivity of the cells to 5-fluorocytosine (5-FC) was determined by MTT assay.

Results: A specific expression of cytosine deaminase gene by adenovirus-mediated transfer exhibited only in SW1990 cells (CEA-producing). Transduction of CD gene resulted in significant sensitivity of SW1990 cells to 5-FC. The anticancer effect was seen in vivo in SW1990 xenografts nude mice with in situ CD gene transduction.

Conclusion: The targeted expression of CD gene combined prodrug 5-FC may be a potential approach for gene therapy for human pancreatic carcinoma.

MeSH terms

  • Adenocarcinoma / therapy*
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / physiology
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Carcinoembryonic Antigen / analysis
  • Carcinoembryonic Antigen / genetics
  • Culture Media
  • Cytosine Deaminase
  • Escherichia coli / enzymology
  • Flucytosine / pharmacology*
  • Gene Expression
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Genetic Vectors / physiology
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy
  • Nucleoside Deaminases / biosynthesis
  • Nucleoside Deaminases / genetics*
  • Pancreatic Neoplasms / therapy*
  • Prodrugs / pharmacology*
  • Promoter Regions, Genetic
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • Carcinoembryonic Antigen
  • Culture Media
  • Prodrugs
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase