Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo

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 tha n 60% of cases of gastric cancer and can lead to genetic instability and un controlled cell. proliferation. The purpose of this investigation was to ev aluate 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 (AdC Ap53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN 1 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 c ell line. The mechanism of the killing of gastric cancer cells by AdCAp53 w as found, by how cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumou rs of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growt h of p53 wild type MKN45 tumours, Conclusions-Adenovirus mediated reintroduction of wild type p53 is a potent ial clinical utility in gene therapy for gastric cancers.