Apoptosis induced by 5-fluorocytosine in human pancreatic cancer cells genetically modified to express cytosine deaminase / 中国病理生理杂志

ABSTRACT

AIM: To elucidate the pattern of 5-fluorocytosine(5-FC) induced apoptosis and its role in gene therapy for human pancreatic cancer. METHODS: The human pancreatic cancer SW1990 cells(CEA-producing) were infected with recombinant adenoviruses(Adex1CEA-prCD or Adex1CEA-prZ).Cytosine deaminase(CD) expression was examind by western blot. Apoptosis induced by 5-FC in human pancreatic cancer SW1990 cells genetically modified to express cytosine deaminase was investigated by applying electron microscopy, DNA electrophoresis and flow cytometry analysis techniques. RESULTS: The SW1990 cells infected with Adex1 CEA-prCD were treated with 5-FC at 100 ?mol?L -1 for 48 h, cell apoptosis occurred. Typical apoptosis morphological feature appeared and DNA ladder could be demonstrated on DNA electrophoresis. Apoptosis peak was also showed by flow cytometry. Apoptotic cells accounted for 34.6% of the cell population. Cells in G 1, S and G 2/M phase of cell cycle were 64%, 11% and 7%, respectively. CONCLUSION: The apoptosis induced by 5-FC may be a primary mechanism in CD gene therapy for pancreatic cancer.