AAV-HGFK1 and Ad-p53 cocktail therapy prolongs survival of mice with colon cancer

Mol Cancer Ther. 2008 Sep;7(9):2855-65. doi: 10.1158/1535-7163.MCT-08-0366.


This study tried to evaluate the application of a novel cancer gene therapy using recombinant adeno-associated virus (AAV) carrying the kringle 1 domain of human hepatocyte growth factor (AAV-HGFK1) in combination with recombinant adenovirus carrying p53 gene (Ad-p53). BALB/c and nude mice models of colon cancer were established and the mice were treated with AAV-HGFK1 alone or in combination with Ad-p53. Combination of AAV-HGFK1 and Ad-p53 significantly prolonged the survival of the mice and also significantly inhibited primary and secondary tumor growth. Histochemical examination of the tumors revealed that AAV-HGFK1+Ad-p53 combinatorial treatment not only induced necrosis and apoptosis in the tumors but also suppressed tumor angiogenesis. The antiangiogenesis effect could likely be attributed to the ability of AAV-HGFK1+Ad-p53 viral cocktail to inhibit endothelial cell migration and proliferation. AAV-HGFK1+Ad-p53 also inhibited tumor cell growth in vitro by inhibiting epidermal growth factor receptor phosphorylation. Therefore, AAV-HGFK1+Ad-p53 cocktail therapy has a significantly higher therapeutic effect than AAV-HGFK1 or Ad-p53 alone and is a novel promising gene therapy for colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Cell Death
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Dependovirus / genetics*
  • Endothelial Cells / pathology
  • Female
  • Genetic Therapy*
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / therapeutic use*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / pathology
  • Survival Analysis
  • Transduction, Genetic
  • Transgenes
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / therapeutic use
  • Xenograft Model Antitumor Assays


  • HGF protein, human
  • Tumor Suppressor Protein p53
  • Hepatocyte Growth Factor