[Enhancement by hypoxia of antisense VEGF(165) gene expression in esophageal cancer cells]

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2002 Sep;34(5):625-9.
[Article in Chinese]

Abstract

To demonstrate effects of antisense VEGF(165) to suppress esophageal cancer cells and to improve efficacy of the gene therapy of tumor by using hypoxic environment, hypoxia response element (HRE) was cloned from promoter of VEGF by PCR and employed to construct an eukaryotic expression vector containing luciferase and antisense VEGF(165) by using recombinant DNA techniques. The recombinant vectors were transfered into esophageal cancer cells by lipofectin methods, and hypoxia inducible reporter gene expression was determined by luminometer and the expression of antisense VEGF was evaluated indirectly by ELISA that detected of VEGF. The esophageal cells tansfected by antisense VEGF(165) gene were transplanted into nude mice, in order to evaluate the suppressive effect of antisense VEGF(165). Our results showed that, in vitro, hypoxia increased expression of reporter gene to 3 780 % and enhanced greatly expression of antisense VEGF. In vivo, the growth of esophageal cancer cells transfected by antisense VEGF in the vector containing HRE was suppressed more significantly, with suppression rate being 71.1%, than that by the vector without HRE, whose inhibiting rate 56.1%. It was concluded that antisense VEGF(165) suppressed significantly growth of esophageal cancer, and by using a gene expression vector containing HRE, the expression of target genes could be regulated autonomously by hypoxic environment of tumor and the efficiency of gene therapy could be greatly improved.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Cell Hypoxia*
  • Disease Models, Animal
  • Endothelial Growth Factors / genetics*
  • Esophageal Neoplasms / physiopathology
  • Eukaryotic Cells
  • Gene Expression Regulation*
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • Luciferases / genetics
  • Lymphokines / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Experimental / physiopathology
  • Oligodeoxyribonucleotides, Antisense*
  • Response Elements
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Oligodeoxyribonucleotides, Antisense
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Luciferases