Enhancement of 5-fluorouracil cytotoxicity on human colon cancer cells by retrovirus-mediated interferon-alpha gene transfer

Gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. Several report s documented the clinical effects of interferon-alpha (IFN-alpha) in manage ment of patients with advanced colorectal carcinoma. We report for the firs t time, the successful transduction of human IFN-alpha gene into colon canc er cells, COLO 201 using a replication-defective retroviral vector. Retrovi rus-containing supernatant from PA 317 packaging cells was used to infect c olon cancer cells, COLO 201 and NIH 3T3 cells. Transient infection showed t hat cell proliferation and cell viability were significantly suppressed in colon cancer cells transduced with IFN-alpha gene. Moreover, IFN-alpha-tran sduced cells acquired less resistance to 5-FU induced apoptosis. These data demonstrate that IFN-alpha gene transfer may have a clinical application a nd can be combined with chemotherapy for treatment of advanced colorectal c ancer.