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Gastrointestinal cancer
Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo
  1. M Ohashia,
  2. F Kanaia,
  3. H Uenob,
  4. T Tanakaa,
  5. K Tateishia,
  6. T Kawakamia,
  7. Y Koikea,
  8. T Ikenouea,
  9. Y Shiratoria,
  10. H Hamadac,
  11. M Omataa
  1. aSecond Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, bResearch Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, cDepartment of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan
  1. Dr M Ohashi.

Abstract

BACKGROUND/AIMS Gastric cancer is one of the most prevalent forms of cancer in East Asia. Point mutation of the p53 gene has been reported in more than 60% of cases of gastric cancer and can lead to genetic instability and uncontrolled cell proliferation. The purpose of this investigation was to evaluate the potential of p53 gene therapy for gastric cancer.

METHODS The responses of human gastric cancer cell lines, MKN1, MKN7, MKN28, MKN45, and TMK-1, to recombinant adenoviruses encoding wild type p53 (AdCAp53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN1 and MKN45 subcutaneous tumours in nude mice was assessed in vivo.

RESULTS p53-specific growth inhibition was observed in vitro in two of four gastric cancer cell lines with mutated p53, but not in the wild type p53 cell line. The mechanism of the killing of gastric cancer cells by AdCAp53 was found, by flow cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumours of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growth of p53 wild type MKN45 tumours.

CONCLUSIONS Adenovirus mediated reintroduction of wild type p53 is a potential clinical utility in gene therapy for gastric cancers.

  • gastric cancer
  • p53
  • adenovirus
  • gene therapy

  • Abbreviations

    moi
    multiplicity of infection
    X-gal
    5-bromo-4-chloro-3-indolyl-β-d- galactopyranoside
    MTT
    3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide

    • https://doi.org/10.1136/gut.44.3.366

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    • Abbreviations

      moi
      multiplicity of infection
      X-gal
      5-bromo-4-chloro-3-indolyl-β-d- galactopyranoside
      MTT
      3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide
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